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Zimei Wu - Academia.edu

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class="onsite-ping" id="onsite-ping"></div></div><div class="profile-user-info DesignSystem"><div class="social-profile-container"><div class="left-panel-container"><div class="user-info-component-wrapper"><div class="user-summary-cta-container"><div class="user-summary-container"><div class="social-profile-avatar-container"><img class="profile-avatar u-positionAbsolute" border="0" alt="" src="//a.academia-assets.com/images/s200_no_pic.png" /></div><div class="title-container"><h1 class="ds2-5-heading-sans-serif-sm">Zimei Wu</h1><div class="affiliations-container fake-truncate js-profile-affiliations"></div></div></div><div class="sidebar-cta-container"><button class="ds2-5-button hidden profile-cta-button grow js-profile-follow-button" data-broccoli-component="user-info.follow-button" data-click-track="profile-user-info-follow-button" data-follow-user-fname="Zimei" data-follow-user-id="53169921" data-follow-user-source="profile_button" data-has-google="false"><span 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href="https://www.academia.edu/115657199/Cyclic_RGDyC_functionalized_liposomes_for_dual_targeting_of_tumor_vasculature_and_cancer_cells_in_glioblastoma_An_in_vitro_boron_neutron_capture_therapy_study"><img alt="Research paper thumbnail of Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study" class="work-thumbnail" src="https://attachments.academia-assets.com/112003665/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/115657199/Cyclic_RGDyC_functionalized_liposomes_for_dual_targeting_of_tumor_vasculature_and_cancer_cells_in_glioblastoma_An_in_vitro_boron_neutron_capture_therapy_study">Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study</a></div><div class="wp-workCard_item"><span>Oncotarget</span><span>, 2017</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2eb598f4c72d88f01d6483e133ffb9e5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:112003665,&quot;asset_id&quot;:115657199,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/112003665/download_file?st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="115657199"><a 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Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a αvβ3 ligand, cyclic arginine-glycine-aspartic acidtyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references. The results showed that both U87 and HUVEC had stronger expression of αvβ3 than other cell types, and the degree of cellular uptake of c(RGDyC)-LP correlated with the αvβ3-expression levels of the cells. In contrast, control liposomes without c(RGDyC) showed little cellular uptake, regardless of cell type. In an in vitro boron neutron capture therapy study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and significant lethal effects to both U87 and HUVEC than the control liposomes and drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different types of subsequent cell death. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277046"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277046/Development_of_Long_Circulating_pH_Sensitive_Liposomes_to_Circumvent_Gemcitabine_Resistance_in_Pancreatic_Cancer_Cells"><img alt="Research paper thumbnail of Development of Long-Circulating pH-Sensitive Liposomes to Circumvent Gemcitabine Resistance in Pancreatic Cancer Cells" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277046/Development_of_Long_Circulating_pH_Sensitive_Liposomes_to_Circumvent_Gemcitabine_Resistance_in_Pancreatic_Cancer_Cells">Development of Long-Circulating pH-Sensitive Liposomes to Circumvent Gemcitabine Resistance in Pancreatic Cancer Cells</a></div><div class="wp-workCard_item"><span>Pharmaceutical Research</span><span>, Mar 10, 2016</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investig...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investigate whether drug loading (DL) would alter the in vitro and pharmacokinetic properties. PSL with a high DL were obtained using a modified small-volume incubation method. The DL effects on drug release rate and in vitro cytotoxicity of PSL were evaluated using MIA PaCa-2 pancreatic cancer cells and their pharmacokinetics investigated in rats. The highest DL of 4.5 ± 0.1% was achieved for gemcitabine in PSL with 145 ± 5 nm diameter. DL did not alter the in vitro release rate from PSL. The IC50 (48 h) of PSL (DL 0.5 and 4.5%) and non pH-sensitive liposomes (NPSL, DL 4.2%) were 1.1 ± 0.1, 0.7 ± 0.1 and 37.0 ± 7.5 μM, respectively. The PSL resulted in a 4.2-fold increase in its elimination half-life (6.2 h) compared to gemcitabine solution (1.4 h) in rats. No significant difference in pharmacokinetic parameters was observed between the two PSL (DL 0.5 and 4.5%). The PSL offered advantages over NPSL in restoring the sensitivity of pancreatic cancer cells to gemcitabine without requiring a high DL. DL in the PSL did not alter release rate, cytotoxicity or their long-circulating properties. Graphical Abstract ᅟ.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277046"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277046"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277046; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277046]").text(description); $(".js-view-count[data-work-id=111277046]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277046; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277046']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277046, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277046]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277046,"title":"Development of Long-Circulating pH-Sensitive Liposomes to Circumvent Gemcitabine Resistance in Pancreatic Cancer Cells","translated_title":"","metadata":{"abstract":"To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investigate whether drug loading (DL) would alter the in vitro and pharmacokinetic properties. PSL with a high DL were obtained using a modified small-volume incubation method. The DL effects on drug release rate and in vitro cytotoxicity of PSL were evaluated using MIA PaCa-2 pancreatic cancer cells and their pharmacokinetics investigated in rats. The highest DL of 4.5 ± 0.1% was achieved for gemcitabine in PSL with 145 ± 5 nm diameter. DL did not alter the in vitro release rate from PSL. The IC50 (48 h) of PSL (DL 0.5 and 4.5%) and non pH-sensitive liposomes (NPSL, DL 4.2%) were 1.1 ± 0.1, 0.7 ± 0.1 and 37.0 ± 7.5 μM, respectively. The PSL resulted in a 4.2-fold increase in its elimination half-life (6.2 h) compared to gemcitabine solution (1.4 h) in rats. No significant difference in pharmacokinetic parameters was observed between the two PSL (DL 0.5 and 4.5%). The PSL offered advantages over NPSL in restoring the sensitivity of pancreatic cancer cells to gemcitabine without requiring a high DL. DL in the PSL did not alter release rate, cytotoxicity or their long-circulating properties. Graphical Abstract ᅟ.","publisher":"Springer Science+Business Media","publication_date":{"day":10,"month":3,"year":2016,"errors":{}},"publication_name":"Pharmaceutical Research"},"translated_abstract":"To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investigate whether drug loading (DL) would alter the in vitro and pharmacokinetic properties. PSL with a high DL were obtained using a modified small-volume incubation method. The DL effects on drug release rate and in vitro cytotoxicity of PSL were evaluated using MIA PaCa-2 pancreatic cancer cells and their pharmacokinetics investigated in rats. The highest DL of 4.5 ± 0.1% was achieved for gemcitabine in PSL with 145 ± 5 nm diameter. DL did not alter the in vitro release rate from PSL. The IC50 (48 h) of PSL (DL 0.5 and 4.5%) and non pH-sensitive liposomes (NPSL, DL 4.2%) were 1.1 ± 0.1, 0.7 ± 0.1 and 37.0 ± 7.5 μM, respectively. The PSL resulted in a 4.2-fold increase in its elimination half-life (6.2 h) compared to gemcitabine solution (1.4 h) in rats. No significant difference in pharmacokinetic parameters was observed between the two PSL (DL 0.5 and 4.5%). The PSL offered advantages over NPSL in restoring the sensitivity of pancreatic cancer cells to gemcitabine without requiring a high DL. DL in the PSL did not alter release rate, cytotoxicity or their long-circulating properties. Graphical Abstract ᅟ.","internal_url":"https://www.academia.edu/111277046/Development_of_Long_Circulating_pH_Sensitive_Liposomes_to_Circumvent_Gemcitabine_Resistance_in_Pancreatic_Cancer_Cells","translated_internal_url":"","created_at":"2023-12-12T16:46:10.086-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Development_of_Long_Circulating_pH_Sensitive_Liposomes_to_Circumvent_Gemcitabine_Resistance_in_Pancreatic_Cancer_Cells","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":26623,"name":"Pancreatic Cancer","url":"https://www.academia.edu/Documents/in/Pancreatic_Cancer"},{"id":59370,"name":"In Vitro","url":"https://www.academia.edu/Documents/in/In_Vitro"},{"id":92788,"name":"Pancreas","url":"https://www.academia.edu/Documents/in/Pancreas"},{"id":95655,"name":"Pharmaceutical","url":"https://www.academia.edu/Documents/in/Pharmaceutical"},{"id":138342,"name":"PSL","url":"https://www.academia.edu/Documents/in/PSL"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":390245,"name":"Particle Size","url":"https://www.academia.edu/Documents/in/Particle_Size"},{"id":1137254,"name":"Hydrogen-Ion Concentration","url":"https://www.academia.edu/Documents/in/Hydrogen-Ion_Concentration"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"},{"id":3521397,"name":"Pancreatic neoplasms","url":"https://www.academia.edu/Documents/in/Pancreatic_neoplasms"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":4132900,"name":"deoxycytidine ","url":"https://www.academia.edu/Documents/in/deoxycytidine"}],"urls":[{"id":36980424,"url":"https://doi.org/10.1007/s11095-016-1902-8"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277045"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277045/Enhanced_pH_Responsiveness_Cellular_Trafficking_Cytotoxicity_and_Long_circulation_of_PEGylated_Liposomes_with_Post_insertion_Technique_Using_Gemcitabine_as_a_Model_Drug"><img alt="Research paper thumbnail of Enhanced pH-Responsiveness, Cellular Trafficking, Cytotoxicity and Long-circulation of PEGylated Liposomes with Post-insertion Technique Using Gemcitabine as a Model Drug" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277045/Enhanced_pH_Responsiveness_Cellular_Trafficking_Cytotoxicity_and_Long_circulation_of_PEGylated_Liposomes_with_Post_insertion_Technique_Using_Gemcitabine_as_a_Model_Drug">Enhanced pH-Responsiveness, Cellular Trafficking, Cytotoxicity and Long-circulation of PEGylated Liposomes with Post-insertion Technique Using Gemcitabine as a Model Drug</a></div><div class="wp-workCard_item"><span>Pharmaceutical Research</span><span>, Feb 6, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The in vitro and in vivo properties of PEGylated pH-sensitive liposomes (PSL) prepared by pre- an...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The in vitro and in vivo properties of PEGylated pH-sensitive liposomes (PSL) prepared by pre- and post-insertion techniques were investigated. A pre-insertion or post-insertion technique was used for PSL PEGylation. For the first time, confocal laser scanning microscopy coupled with a modified calcein self-quench assay was applied to evaluate the endosome escape capability. PSL cellular uptake was evaluated using macrophages and the cytotoxicity using a gemcitabine (model drug)-resistant MIA PaCa-2 cells. The pharmacokinetics of PSL encapsulated gemcitabine was investigated in rats. PEGylation reduced the pH-sensitivity in a concentration-dependent manner (0.5-5% mol). Both PEGylation methods reduced the uptake of PSL by macrophages by over 60%. Cytotoxicity was ranked in the order: post-inserted PSL ≥ pre-inserted PSL &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; non-PSL &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; gemcitabine solution, consistent with the confocal microscopic observation and pH-sensitivity. Both pre and post-inserted PSL resulted in significant reductions (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) in plasma clearance (58.6 and 38.4 ml/h/kg), increases in the area-under-the-concentration-time curve (56.9 and 87.1 μM· h) and half-life (6.1 and 6.2 h) compared to gemcitabine solution (152.9 ml/h/kg, 22.2 μM· h and 1.4 h). PEGylation by post-insertion offers advantages over pre-insertion to obtain PSL with enhanced pH-sensitivity, more effective intra-cytoplasmic delivery, and a superior pharmacokinetics.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277045"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277045"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277045; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277045]").text(description); $(".js-view-count[data-work-id=111277045]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277045; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277045']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277045, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277045]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277045,"title":"Enhanced pH-Responsiveness, Cellular Trafficking, Cytotoxicity and Long-circulation of PEGylated Liposomes with Post-insertion Technique Using Gemcitabine as a Model Drug","translated_title":"","metadata":{"abstract":"The in vitro and in vivo properties of PEGylated pH-sensitive liposomes (PSL) prepared by pre- and post-insertion techniques were investigated. A pre-insertion or post-insertion technique was used for PSL PEGylation. For the first time, confocal laser scanning microscopy coupled with a modified calcein self-quench assay was applied to evaluate the endosome escape capability. PSL cellular uptake was evaluated using macrophages and the cytotoxicity using a gemcitabine (model drug)-resistant MIA PaCa-2 cells. The pharmacokinetics of PSL encapsulated gemcitabine was investigated in rats. PEGylation reduced the pH-sensitivity in a concentration-dependent manner (0.5-5% mol). Both PEGylation methods reduced the uptake of PSL by macrophages by over 60%. Cytotoxicity was ranked in the order: post-inserted PSL ≥ pre-inserted PSL \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; non-PSL \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; gemcitabine solution, consistent with the confocal microscopic observation and pH-sensitivity. Both pre and post-inserted PSL resulted in significant reductions (p \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) in plasma clearance (58.6 and 38.4 ml/h/kg), increases in the area-under-the-concentration-time curve (56.9 and 87.1 μM· h) and half-life (6.1 and 6.2 h) compared to gemcitabine solution (152.9 ml/h/kg, 22.2 μM· h and 1.4 h). PEGylation by post-insertion offers advantages over pre-insertion to obtain PSL with enhanced pH-sensitivity, more effective intra-cytoplasmic delivery, and a superior pharmacokinetics.","publisher":"Springer Science+Business Media","publication_date":{"day":6,"month":2,"year":2015,"errors":{}},"publication_name":"Pharmaceutical Research"},"translated_abstract":"The in vitro and in vivo properties of PEGylated pH-sensitive liposomes (PSL) prepared by pre- and post-insertion techniques were investigated. A pre-insertion or post-insertion technique was used for PSL PEGylation. For the first time, confocal laser scanning microscopy coupled with a modified calcein self-quench assay was applied to evaluate the endosome escape capability. PSL cellular uptake was evaluated using macrophages and the cytotoxicity using a gemcitabine (model drug)-resistant MIA PaCa-2 cells. The pharmacokinetics of PSL encapsulated gemcitabine was investigated in rats. PEGylation reduced the pH-sensitivity in a concentration-dependent manner (0.5-5% mol). Both PEGylation methods reduced the uptake of PSL by macrophages by over 60%. Cytotoxicity was ranked in the order: post-inserted PSL ≥ pre-inserted PSL \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; non-PSL \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; gemcitabine solution, consistent with the confocal microscopic observation and pH-sensitivity. Both pre and post-inserted PSL resulted in significant reductions (p \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) in plasma clearance (58.6 and 38.4 ml/h/kg), increases in the area-under-the-concentration-time curve (56.9 and 87.1 μM· h) and half-life (6.1 and 6.2 h) compared to gemcitabine solution (152.9 ml/h/kg, 22.2 μM· h and 1.4 h). PEGylation by post-insertion offers advantages over pre-insertion to obtain PSL with enhanced pH-sensitivity, more effective intra-cytoplasmic delivery, and a superior pharmacokinetics.","internal_url":"https://www.academia.edu/111277045/Enhanced_pH_Responsiveness_Cellular_Trafficking_Cytotoxicity_and_Long_circulation_of_PEGylated_Liposomes_with_Post_insertion_Technique_Using_Gemcitabine_as_a_Model_Drug","translated_internal_url":"","created_at":"2023-12-12T16:46:09.842-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Enhanced_pH_Responsiveness_Cellular_Trafficking_Cytotoxicity_and_Long_circulation_of_PEGylated_Liposomes_with_Post_insertion_Technique_Using_Gemcitabine_as_a_Model_Drug","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":11257,"name":"Drug delivery","url":"https://www.academia.edu/Documents/in/Drug_delivery"},{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":90156,"name":"Endocytosis","url":"https://www.academia.edu/Documents/in/Endocytosis"},{"id":95655,"name":"Pharmaceutical","url":"https://www.academia.edu/Documents/in/Pharmaceutical"},{"id":129181,"name":"PEGylation","url":"https://www.academia.edu/Documents/in/PEGylation"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":302037,"name":"In Vivo","url":"https://www.academia.edu/Documents/in/In_Vivo"},{"id":390245,"name":"Particle Size","url":"https://www.academia.edu/Documents/in/Particle_Size"},{"id":1031068,"name":"Drug Carriers","url":"https://www.academia.edu/Documents/in/Drug_Carriers"},{"id":1135812,"name":"Drug Compounding","url":"https://www.academia.edu/Documents/in/Drug_Compounding"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1254280,"name":"Endosomes","url":"https://www.academia.edu/Documents/in/Endosomes"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"}],"urls":[{"id":36980423,"url":"https://doi.org/10.1007/s11095-015-1635-0"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277044"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277044/Development_of_High_Content_Gemcitabine_PEGylated_Liposomes_and_Their_Cytotoxicity_on_Drug_Resistant_Pancreatic_Tumour_Cells"><img alt="Research paper thumbnail of Development of High-Content Gemcitabine PEGylated Liposomes and Their Cytotoxicity on Drug-Resistant Pancreatic Tumour Cells" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277044/Development_of_High_Content_Gemcitabine_PEGylated_Liposomes_and_Their_Cytotoxicity_on_Drug_Resistant_Pancreatic_Tumour_Cells">Development of High-Content Gemcitabine PEGylated Liposomes and Their Cytotoxicity on Drug-Resistant Pancreatic Tumour Cells</a></div><div class="wp-workCard_item"><span>Pharmaceutical Research</span><span>, Mar 18, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The objective of this study was to develop high-content gemcitabine PEGylated liposomes to revers...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The objective of this study was to develop high-content gemcitabine PEGylated liposomes to reverse gemcitabine resistance in pancreatic tumour cells. The mechanism of drug loading into liposomes was also investigated. To increase the drug entrapment efficiency (EE) and drug loading (DL), a novel passive loading approach named Small Volume Incubation method (SVI) was developed and compared to the reverse phase evaporation (REV) and remote loading methods. The in vitro cytotoxicity was evaluated using MIA PaCa-2 and Panc-1 cell lines. The EE for remote loading was 12.3 ± 0.3%, much lower than expected and a burst release was observed with the resultant liposomes. Using the optimized SVI method, increased EE (37 ± 1%) and DL (4%, w/w) were obtained. The liposomes (200 ± 5 nm) showed minimal drug leakage, good stability, and significant improvement in cytotoxicity to the gemcitabine-resistant pancreatic cancer cell lines. Remote loading was not suitable for loading gemcitabine into liposomes. pKa &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4.6 for basic drugs and intra-liposomal precipitation of loaded compounds were suggested as an additional requirement to the current criteria for remote loading using ammonium sulphate gradient (pKa &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 11). High DL is essential for liposomes to reverse gemcitabine resistance in pancreatic cell lines.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277044"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277044"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277044; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277044]").text(description); $(".js-view-count[data-work-id=111277044]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277044; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277044']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277044, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277044]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277044,"title":"Development of High-Content Gemcitabine PEGylated Liposomes and Their Cytotoxicity on Drug-Resistant Pancreatic Tumour Cells","translated_title":"","metadata":{"abstract":"The objective of this study was to develop high-content gemcitabine PEGylated liposomes to reverse gemcitabine resistance in pancreatic tumour cells. The mechanism of drug loading into liposomes was also investigated. To increase the drug entrapment efficiency (EE) and drug loading (DL), a novel passive loading approach named Small Volume Incubation method (SVI) was developed and compared to the reverse phase evaporation (REV) and remote loading methods. The in vitro cytotoxicity was evaluated using MIA PaCa-2 and Panc-1 cell lines. The EE for remote loading was 12.3 ± 0.3%, much lower than expected and a burst release was observed with the resultant liposomes. Using the optimized SVI method, increased EE (37 ± 1%) and DL (4%, w/w) were obtained. The liposomes (200 ± 5 nm) showed minimal drug leakage, good stability, and significant improvement in cytotoxicity to the gemcitabine-resistant pancreatic cancer cell lines. Remote loading was not suitable for loading gemcitabine into liposomes. pKa \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4.6 for basic drugs and intra-liposomal precipitation of loaded compounds were suggested as an additional requirement to the current criteria for remote loading using ammonium sulphate gradient (pKa \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 11). High DL is essential for liposomes to reverse gemcitabine resistance in pancreatic cell lines.","publisher":"Springer Science+Business Media","publication_date":{"day":18,"month":3,"year":2014,"errors":{}},"publication_name":"Pharmaceutical Research"},"translated_abstract":"The objective of this study was to develop high-content gemcitabine PEGylated liposomes to reverse gemcitabine resistance in pancreatic tumour cells. The mechanism of drug loading into liposomes was also investigated. To increase the drug entrapment efficiency (EE) and drug loading (DL), a novel passive loading approach named Small Volume Incubation method (SVI) was developed and compared to the reverse phase evaporation (REV) and remote loading methods. The in vitro cytotoxicity was evaluated using MIA PaCa-2 and Panc-1 cell lines. The EE for remote loading was 12.3 ± 0.3%, much lower than expected and a burst release was observed with the resultant liposomes. Using the optimized SVI method, increased EE (37 ± 1%) and DL (4%, w/w) were obtained. The liposomes (200 ± 5 nm) showed minimal drug leakage, good stability, and significant improvement in cytotoxicity to the gemcitabine-resistant pancreatic cancer cell lines. Remote loading was not suitable for loading gemcitabine into liposomes. pKa \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4.6 for basic drugs and intra-liposomal precipitation of loaded compounds were suggested as an additional requirement to the current criteria for remote loading using ammonium sulphate gradient (pKa \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 11). High DL is essential for liposomes to reverse gemcitabine resistance in pancreatic cell lines.","internal_url":"https://www.academia.edu/111277044/Development_of_High_Content_Gemcitabine_PEGylated_Liposomes_and_Their_Cytotoxicity_on_Drug_Resistant_Pancreatic_Tumour_Cells","translated_internal_url":"","created_at":"2023-12-12T16:46:09.585-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Development_of_High_Content_Gemcitabine_PEGylated_Liposomes_and_Their_Cytotoxicity_on_Drug_Resistant_Pancreatic_Tumour_Cells","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":9186,"name":"Pharmaceutical Technology","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Technology"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":26623,"name":"Pancreatic Cancer","url":"https://www.academia.edu/Documents/in/Pancreatic_Cancer"},{"id":95655,"name":"Pharmaceutical","url":"https://www.academia.edu/Documents/in/Pharmaceutical"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":390245,"name":"Particle Size","url":"https://www.academia.edu/Documents/in/Particle_Size"},{"id":405347,"name":"Pharmaceutical Formulation Technology","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Formulation_Technology"},{"id":440924,"name":"Surface Properties","url":"https://www.academia.edu/Documents/in/Surface_Properties"},{"id":1031068,"name":"Drug Carriers","url":"https://www.academia.edu/Documents/in/Drug_Carriers"},{"id":1135812,"name":"Drug Compounding","url":"https://www.academia.edu/Documents/in/Drug_Compounding"},{"id":1135814,"name":"Drug Stability","url":"https://www.academia.edu/Documents/in/Drug_Stability"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"},{"id":1434630,"name":"Polyethylene Glycols","url":"https://www.academia.edu/Documents/in/Polyethylene_Glycols"},{"id":3521397,"name":"Pancreatic neoplasms","url":"https://www.academia.edu/Documents/in/Pancreatic_neoplasms"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":4132900,"name":"deoxycytidine ","url":"https://www.academia.edu/Documents/in/deoxycytidine"}],"urls":[{"id":36980422,"url":"https://doi.org/10.1007/s11095-014-1353-z"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277043"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277043/Brain_targeted_intranasal_delivery_of_dopamine_with_borneol_and_lactoferrin_co_modified_nanoparticles_for_treating_Parkinson_s_disease"><img alt="Research paper thumbnail of Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease" class="work-thumbnail" src="https://attachments.academia-assets.com/108858257/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277043/Brain_targeted_intranasal_delivery_of_dopamine_with_borneol_and_lactoferrin_co_modified_nanoparticles_for_treating_Parkinson_s_disease">Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease</a></div><div class="wp-workCard_item"><span>Drug Delivery</span><span>, 2019</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1834a5802a825d5cc6ac193c8b583185" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858257,&quot;asset_id&quot;:111277043,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858257/download_file?st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277043"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277043"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277043; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277043]").text(description); $(".js-view-count[data-work-id=111277043]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277043; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277043']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277043, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "1834a5802a825d5cc6ac193c8b583185" } } $('.js-work-strip[data-work-id=111277043]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277043,"title":"Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease","translated_title":"","metadata":{"publisher":"Informa UK Limited","grobid_abstract":"Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC 0-12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p \u003c .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson's disease.","publication_date":{"day":null,"month":null,"year":2019,"errors":{}},"publication_name":"Drug Delivery","grobid_abstract_attachment_id":108858257},"translated_abstract":null,"internal_url":"https://www.academia.edu/111277043/Brain_targeted_intranasal_delivery_of_dopamine_with_borneol_and_lactoferrin_co_modified_nanoparticles_for_treating_Parkinson_s_disease","translated_internal_url":"","created_at":"2023-12-12T16:46:09.178-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858257,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858257/thumbnails/1.jpg","file_name":"10717544.2019.pdf","download_url":"https://www.academia.edu/attachments/108858257/download_file?st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Brain_targeted_intranasal_delivery_of_do.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858257/10717544.2019-libre.pdf?1702428630=\u0026response-content-disposition=attachment%3B+filename%3DBrain_targeted_intranasal_delivery_of_do.pdf\u0026Expires=1732823519\u0026Signature=UxCWQ4idnM47VttJznWILMf-JH51f3tQAWEavrRwyUg2aNkxUqBXDEPrY6nZ45LvatpDHPYTB1icbdN0TE9WGbqu6s9UQwagfe8m9l-ePRDTA8RC9ShMrQWh~ogdbaNGRUb~ZlhXCHgDUu0gqx8PebX~Rfqb1115h3GYLp2kVxd2BDNjDwknfp9RsWNqA17rC9q0nbH0SvMSWNhG1LDV2hx2grRV2Y~L5o3lVZdbd9y-SqKu8Ot5HzdT4Lmkb1MXfBnUWI6tPL~6DWlSrY0be7TkPX5yojMF3maROLpnl11m23mgZ8MmwbASeO7sgBoBBUc71a~fKSYDSgMAil1iqw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Brain_targeted_intranasal_delivery_of_dopamine_with_borneol_and_lactoferrin_co_modified_nanoparticles_for_treating_Parkinson_s_disease","translated_slug":"","page_count":9,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858257,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858257/thumbnails/1.jpg","file_name":"10717544.2019.pdf","download_url":"https://www.academia.edu/attachments/108858257/download_file?st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Brain_targeted_intranasal_delivery_of_do.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858257/10717544.2019-libre.pdf?1702428630=\u0026response-content-disposition=attachment%3B+filename%3DBrain_targeted_intranasal_delivery_of_do.pdf\u0026Expires=1732823519\u0026Signature=UxCWQ4idnM47VttJznWILMf-JH51f3tQAWEavrRwyUg2aNkxUqBXDEPrY6nZ45LvatpDHPYTB1icbdN0TE9WGbqu6s9UQwagfe8m9l-ePRDTA8RC9ShMrQWh~ogdbaNGRUb~ZlhXCHgDUu0gqx8PebX~Rfqb1115h3GYLp2kVxd2BDNjDwknfp9RsWNqA17rC9q0nbH0SvMSWNhG1LDV2hx2grRV2Y~L5o3lVZdbd9y-SqKu8Ot5HzdT4Lmkb1MXfBnUWI6tPL~6DWlSrY0be7TkPX5yojMF3maROLpnl11m23mgZ8MmwbASeO7sgBoBBUc71a~fKSYDSgMAil1iqw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":11257,"name":"Drug delivery","url":"https://www.academia.edu/Documents/in/Drug_delivery"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":51566,"name":"Dopamine","url":"https://www.academia.edu/Documents/in/Dopamine"},{"id":302037,"name":"In Vivo","url":"https://www.academia.edu/Documents/in/In_Vivo"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980421,"url":"https://tandfonline.com/doi/pdf/10.1080/10717544.2019.1636420"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277042"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277042/Liposome_supported_peritoneal_dialysis_in_rat_amitriptyline_exposure_with_and_without_intravenous_lipid_emulsion"><img alt="Research paper thumbnail of Liposome supported peritoneal dialysis in rat amitriptyline exposure with and without intravenous lipid emulsion" class="work-thumbnail" src="https://attachments.academia-assets.com/108858256/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277042/Liposome_supported_peritoneal_dialysis_in_rat_amitriptyline_exposure_with_and_without_intravenous_lipid_emulsion">Liposome supported peritoneal dialysis in rat amitriptyline exposure with and without intravenous lipid emulsion</a></div><div class="wp-workCard_item"><span>Journal of liposome research</span><span>, Jan 5, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Liposome supported peritoneal dialysis is a recently described technique which may eventually be ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Liposome supported peritoneal dialysis is a recently described technique which may eventually be applicable in the clinical scenario of the intoxicated patient. We evaluated the hypothesis that intravenous injection of lipid emulsion (ILE) would augment acidic pH gradient liposome supported peritoneal dialysis (LSPD). Orogastrically amitriptyline dosed rats were treated with either Sodium bicarbonate (NaHCO3) intravenously and standard intraperitoneal dialysate (Group A); NaHCO3 intravenously and LSPD (Group B); or ILE and LSPD (Group C). The primary endpoint was dialysate amitriptyline concentration after a 60 min dwell. Secondary analysis included an estimate of extraction ratio for peritoneal blood flow (ERs). There were significantly higher intraperitoneal concentrations of amitriptyline and ERs in the two groups treated with LSPD (Group B, p = 0.02, Group C, p &amp;lt; 0.01 vs. Group A). There was no observed effect for ILE on intraperitoneal amitriptyline concentration or ERs (p &amp;...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="8148ad461ceb427f0d0e98b37a4d191e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858256,&quot;asset_id&quot;:111277042,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858256/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277042"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277042"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277042; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277042]").text(description); $(".js-view-count[data-work-id=111277042]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277042; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277042']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277042, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "8148ad461ceb427f0d0e98b37a4d191e" } } $('.js-work-strip[data-work-id=111277042]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277042,"title":"Liposome supported peritoneal dialysis in rat amitriptyline exposure with and without intravenous lipid emulsion","translated_title":"","metadata":{"abstract":"Liposome supported peritoneal dialysis is a recently described technique which may eventually be applicable in the clinical scenario of the intoxicated patient. We evaluated the hypothesis that intravenous injection of lipid emulsion (ILE) would augment acidic pH gradient liposome supported peritoneal dialysis (LSPD). Orogastrically amitriptyline dosed rats were treated with either Sodium bicarbonate (NaHCO3) intravenously and standard intraperitoneal dialysate (Group A); NaHCO3 intravenously and LSPD (Group B); or ILE and LSPD (Group C). The primary endpoint was dialysate amitriptyline concentration after a 60 min dwell. Secondary analysis included an estimate of extraction ratio for peritoneal blood flow (ERs). There were significantly higher intraperitoneal concentrations of amitriptyline and ERs in the two groups treated with LSPD (Group B, p = 0.02, Group C, p \u0026lt; 0.01 vs. Group A). There was no observed effect for ILE on intraperitoneal amitriptyline concentration or ERs (p \u0026...","publication_date":{"day":5,"month":1,"year":2017,"errors":{}},"publication_name":"Journal of liposome research"},"translated_abstract":"Liposome supported peritoneal dialysis is a recently described technique which may eventually be applicable in the clinical scenario of the intoxicated patient. We evaluated the hypothesis that intravenous injection of lipid emulsion (ILE) would augment acidic pH gradient liposome supported peritoneal dialysis (LSPD). Orogastrically amitriptyline dosed rats were treated with either Sodium bicarbonate (NaHCO3) intravenously and standard intraperitoneal dialysate (Group A); NaHCO3 intravenously and LSPD (Group B); or ILE and LSPD (Group C). The primary endpoint was dialysate amitriptyline concentration after a 60 min dwell. Secondary analysis included an estimate of extraction ratio for peritoneal blood flow (ERs). There were significantly higher intraperitoneal concentrations of amitriptyline and ERs in the two groups treated with LSPD (Group B, p = 0.02, Group C, p \u0026lt; 0.01 vs. Group A). There was no observed effect for ILE on intraperitoneal amitriptyline concentration or ERs (p \u0026...","internal_url":"https://www.academia.edu/111277042/Liposome_supported_peritoneal_dialysis_in_rat_amitriptyline_exposure_with_and_without_intravenous_lipid_emulsion","translated_internal_url":"","created_at":"2023-12-12T16:46:08.991-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858256,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858256/thumbnails/1.jpg","file_name":"15191549.pdf","download_url":"https://www.academia.edu/attachments/108858256/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Liposome_supported_peritoneal_dialysis_i.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858256/15191549-libre.pdf?1702428624=\u0026response-content-disposition=attachment%3B+filename%3DLiposome_supported_peritoneal_dialysis_i.pdf\u0026Expires=1732823520\u0026Signature=S1K~y-On4eZ-cwtlUQM9Dax5TLXmSAny8DUtV3rQ9FnjCF6fyiIEgc3qB~tBml5q2NjCiZ2O2IDNVj09577X6tfI3KKm1sEyawNjbmPaubmMw~n5k-knj576qEGkW6HoENMkfS17FhUCHu9ksSQ-B3ACIZVPv~WFP4yi-Z~qP7AK9ItlC7UYeLWxU6Zsw-8EFGBnE7rGdAr14Hw80xvnbcmIqkrscGBOmxAI4RQdPuFaD-VpGlnNVsuPonVPSQwJBvyVHXJIkyctVxvcT5jF8PmtYrkuOBbKP7ovQwtqvm6bKN196EsCy-zPwAqvLoY4gmEPI5aOZq5VXBqM8w9c0g__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Liposome_supported_peritoneal_dialysis_in_rat_amitriptyline_exposure_with_and_without_intravenous_lipid_emulsion","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858256,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858256/thumbnails/1.jpg","file_name":"15191549.pdf","download_url":"https://www.academia.edu/attachments/108858256/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Liposome_supported_peritoneal_dialysis_i.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858256/15191549-libre.pdf?1702428624=\u0026response-content-disposition=attachment%3B+filename%3DLiposome_supported_peritoneal_dialysis_i.pdf\u0026Expires=1732823520\u0026Signature=S1K~y-On4eZ-cwtlUQM9Dax5TLXmSAny8DUtV3rQ9FnjCF6fyiIEgc3qB~tBml5q2NjCiZ2O2IDNVj09577X6tfI3KKm1sEyawNjbmPaubmMw~n5k-knj576qEGkW6HoENMkfS17FhUCHu9ksSQ-B3ACIZVPv~WFP4yi-Z~qP7AK9ItlC7UYeLWxU6Zsw-8EFGBnE7rGdAr14Hw80xvnbcmIqkrscGBOmxAI4RQdPuFaD-VpGlnNVsuPonVPSQwJBvyVHXJIkyctVxvcT5jF8PmtYrkuOBbKP7ovQwtqvm6bKN196EsCy-zPwAqvLoY4gmEPI5aOZq5VXBqM8w9c0g__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":145,"name":"Biochemistry","url":"https://www.academia.edu/Documents/in/Biochemistry"},{"id":158,"name":"Marine Biology","url":"https://www.academia.edu/Documents/in/Marine_Biology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":1524,"name":"Science Policy","url":"https://www.academia.edu/Documents/in/Science_Policy"},{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":4553,"name":"Toxicology","url":"https://www.academia.edu/Documents/in/Toxicology"},{"id":5398,"name":"Biotechnology","url":"https://www.academia.edu/Documents/in/Biotechnology"},{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer"},{"id":13827,"name":"Cell Biology","url":"https://www.academia.edu/Documents/in/Cell_Biology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":447741,"name":"Peritoneal Dialysis","url":"https://www.academia.edu/Documents/in/Peritoneal_Dialysis"},{"id":1508487,"name":"Amitriptyline","url":"https://www.academia.edu/Documents/in/Amitriptyline"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277041"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277041/Effects_of_GHK_Cu_on_MMP_and_TIMP_Expression_Collagen_and_Elastin_Production_and_Facial_Wrinkle_Parameters"><img alt="Research paper thumbnail of Effects of GHK-Cu on MMP and TIMP Expression, Collagen and Elastin Production, and Facial Wrinkle Parameters" class="work-thumbnail" src="https://attachments.academia-assets.com/108858255/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277041/Effects_of_GHK_Cu_on_MMP_and_TIMP_Expression_Collagen_and_Elastin_Production_and_Facial_Wrinkle_Parameters">Effects of GHK-Cu on MMP and TIMP Expression, Collagen and Elastin Production, and Facial Wrinkle Parameters</a></div><div class="wp-workCard_item"><span>Journal of Aging Science</span><span>, 2016</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5f2a15fd11f9b407665659fedac45e31" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858255,&quot;asset_id&quot;:111277041,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858255/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277041"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277041"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277041; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277041]").text(description); $(".js-view-count[data-work-id=111277041]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277041; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277041']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277041, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5f2a15fd11f9b407665659fedac45e31" } } $('.js-work-strip[data-work-id=111277041]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277041,"title":"Effects of GHK-Cu on MMP and TIMP Expression, Collagen and Elastin Production, and Facial Wrinkle Parameters","translated_title":"","metadata":{"publisher":"OMICS Publishing Group","grobid_abstract":"Background: Glycyl-L-histidyl-L-lysine-copper (GHK-Cu) is an endogenous tripeptide-copper complex involved in collagen synthesis and is used topically as a skin anti-aging and wound healing agent. However, its biological effects are yet to be fully elucidated. Objectives: To investigate the effects of GHK-Cu on gene expression of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), and on production of collagen and elastin by human adult dermal fibroblasts (HDFa); and to investigate the effectiveness of topical application of GHK-Cu on wrinkle parameters in volunteers. Methods: Cultured HDFa were incubated with GHK-Cu at 0.01, 1 and 100 nM in cell culture medium. Gene expression (mRNA) for MMP1, MMP2, TIMP1 and TIMP2 in treated and control HDFa was measured by RT-PCR. Cellular production of collagen and elastin was measured colourmetrically using commercial assay kits. Correlations between gene expression and collagen and elastin production were determined. A randomised, double-blind clinical trial involving twice daily application of GHK-Cu, encapsulated in lipid-based nano-carrier, to facial skin of female subjects (n= 40, aged 40 to 65) was run over 8 weeks. The formulation vehicle (a serum) and a commercial cosmetic product containing Matrixyl ® 3000, a lipophilic GHK derivative, were used as controls. Results: GHK-Cu significantly increased gene expression of MMP1 and MMP2 at the lowest concentration whilst simultaneously increasing the expression of TIMP1 at all the tested concentrations. All examined concentrations of GHK-Cu increased both collagen and elastin production. An increase of the mRNA expression ratio of TIMPs to MMPs was associated with an increase in collagen/elastin production. Application of GHK-Cu in nano-carriers to facial skin of volunteers significantly reduced wrinkle volume (31.6%; p=0.004) compared to Matrixyl ® 3000, and significantly reduced wrinkle volume (55.8%; p\u003c0.001) and wrinkle depth (32.8%; p=0.012) compared to control serum. Conclusions: GHK-Cu significantly increased collagen and elastin production by HDFa cells depending on the relative mRNA expression of their TIMP(s) over MMP. Topical application of GHK-Cu with the aid of nano-carriers reduced wrinkle volume to a significantly greater extent than the vehicle alone or a commercial product containing Matrixyl 3000 ® , a GHK lipophilic derivative.","publication_date":{"day":null,"month":null,"year":2016,"errors":{}},"publication_name":"Journal of Aging Science","grobid_abstract_attachment_id":108858255},"translated_abstract":null,"internal_url":"https://www.academia.edu/111277041/Effects_of_GHK_Cu_on_MMP_and_TIMP_Expression_Collagen_and_Elastin_Production_and_Facial_Wrinkle_Parameters","translated_internal_url":"","created_at":"2023-12-12T16:46:08.842-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858255,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858255/thumbnails/1.jpg","file_name":"4298d633ec602468b9b43d1730baede1de5d.pdf","download_url":"https://www.academia.edu/attachments/108858255/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effects_of_GHK_Cu_on_MMP_and_TIMP_Expres.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858255/4298d633ec602468b9b43d1730baede1de5d-libre.pdf?1702428639=\u0026response-content-disposition=attachment%3B+filename%3DEffects_of_GHK_Cu_on_MMP_and_TIMP_Expres.pdf\u0026Expires=1732823520\u0026Signature=X5pj-7M6~9WO4eh4tzD7~XiC21vL-QmnJGZJgnRVxitmeECymbcT1VFXuVj-jiaqYYHs41f~LgVm-MZ1E2ebY2DTRjzsXFpvQ80CD9C63krq6guKf0fx7zQNCN7mQOgOZ8ELm0Ymfz9ZU-DC~pkWbo2qVpjG~tEzo-vYBFpVWJWXTHNbDpAxp05mP1~Eiaco~-eIz-0a9Xy82eITbPRMmdXrR8rKVeper1wNLK1P0e8hOlUMZyFv3i8QmGuN4krmikb96f0~Q1QxkEyExgxSdKBqvlbTWTvaypetOsWjvGeyDj2pyf0GvQTLP7lepnPoXLA0nVOwYkfakbQ7VcRT-A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Effects_of_GHK_Cu_on_MMP_and_TIMP_Expression_Collagen_and_Elastin_Production_and_Facial_Wrinkle_Parameters","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858255,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858255/thumbnails/1.jpg","file_name":"4298d633ec602468b9b43d1730baede1de5d.pdf","download_url":"https://www.academia.edu/attachments/108858255/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effects_of_GHK_Cu_on_MMP_and_TIMP_Expres.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858255/4298d633ec602468b9b43d1730baede1de5d-libre.pdf?1702428639=\u0026response-content-disposition=attachment%3B+filename%3DEffects_of_GHK_Cu_on_MMP_and_TIMP_Expres.pdf\u0026Expires=1732823520\u0026Signature=X5pj-7M6~9WO4eh4tzD7~XiC21vL-QmnJGZJgnRVxitmeECymbcT1VFXuVj-jiaqYYHs41f~LgVm-MZ1E2ebY2DTRjzsXFpvQ80CD9C63krq6guKf0fx7zQNCN7mQOgOZ8ELm0Ymfz9ZU-DC~pkWbo2qVpjG~tEzo-vYBFpVWJWXTHNbDpAxp05mP1~Eiaco~-eIz-0a9Xy82eITbPRMmdXrR8rKVeper1wNLK1P0e8hOlUMZyFv3i8QmGuN4krmikb96f0~Q1QxkEyExgxSdKBqvlbTWTvaypetOsWjvGeyDj2pyf0GvQTLP7lepnPoXLA0nVOwYkfakbQ7VcRT-A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":350926,"name":"Elastin","url":"https://www.academia.edu/Documents/in/Elastin"},{"id":1920779,"name":"Matrix Metalloproteinase","url":"https://www.academia.edu/Documents/in/Matrix_Metalloproteinase"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277040"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277040/Reversal_of_lipophilic_weak_bases_using_pH_gradient_acidic_centre_liposomes_demonstration_of_effect_in_dabigatran_induced_anticoagulation"><img alt="Research paper thumbnail of Reversal of lipophilic weak bases using pH gradient acidic centre liposomes: demonstration of effect in dabigatran-induced anticoagulation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277040/Reversal_of_lipophilic_weak_bases_using_pH_gradient_acidic_centre_liposomes_demonstration_of_effect_in_dabigatran_induced_anticoagulation">Reversal of lipophilic weak bases using pH gradient acidic centre liposomes: demonstration of effect in dabigatran-induced anticoagulation</a></div><div class="wp-workCard_item"><span>Clinical toxicology (Philadelphia, Pa.)</span><span>, Jan 29, 2016</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Liposomes have recently emerged as rational vehicles for drug detoxification. Modification of the...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Liposomes have recently emerged as rational vehicles for drug detoxification. Modification of the core pH may further enhance the ability of liposomes to sequester lipophilic toxins that are weak bases. Dabigatran, a reversible inhibitor of thrombin, has been widely promoted as a novel oral anticoagulant. As a lipophilic weak-base, it provides a rational target for reversal with acidic-centred liposomal preparations. The present study tests the hypothesis that acidic centre liposomes will reverse dabigatran induced anticoagulation. Following enteric dabigatran dosing in vitro assessment of thrombin clotting times (TCT) was undertaken in rabbit plasma spiked with incremental liposome concentrations. Tail vein bleeding was assessed following intravenous liposome injection in rats after enteric dabigatran administration. Liposomes achieved reversal of TCT to baseline at low levels of thrombin inhibition, and partial reversal of TCT at higher levels. Liposomes completely reversed the ef...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277040"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277040"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277040; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277040]").text(description); $(".js-view-count[data-work-id=111277040]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277040; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277040']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277040, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277040]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277040,"title":"Reversal of lipophilic weak bases using pH gradient acidic centre liposomes: demonstration of effect in dabigatran-induced anticoagulation","translated_title":"","metadata":{"abstract":"Liposomes have recently emerged as rational vehicles for drug detoxification. Modification of the core pH may further enhance the ability of liposomes to sequester lipophilic toxins that are weak bases. Dabigatran, a reversible inhibitor of thrombin, has been widely promoted as a novel oral anticoagulant. As a lipophilic weak-base, it provides a rational target for reversal with acidic-centred liposomal preparations. The present study tests the hypothesis that acidic centre liposomes will reverse dabigatran induced anticoagulation. Following enteric dabigatran dosing in vitro assessment of thrombin clotting times (TCT) was undertaken in rabbit plasma spiked with incremental liposome concentrations. Tail vein bleeding was assessed following intravenous liposome injection in rats after enteric dabigatran administration. Liposomes achieved reversal of TCT to baseline at low levels of thrombin inhibition, and partial reversal of TCT at higher levels. Liposomes completely reversed the ef...","publication_date":{"day":29,"month":1,"year":2016,"errors":{}},"publication_name":"Clinical toxicology (Philadelphia, Pa.)"},"translated_abstract":"Liposomes have recently emerged as rational vehicles for drug detoxification. Modification of the core pH may further enhance the ability of liposomes to sequester lipophilic toxins that are weak bases. Dabigatran, a reversible inhibitor of thrombin, has been widely promoted as a novel oral anticoagulant. As a lipophilic weak-base, it provides a rational target for reversal with acidic-centred liposomal preparations. The present study tests the hypothesis that acidic centre liposomes will reverse dabigatran induced anticoagulation. Following enteric dabigatran dosing in vitro assessment of thrombin clotting times (TCT) was undertaken in rabbit plasma spiked with incremental liposome concentrations. Tail vein bleeding was assessed following intravenous liposome injection in rats after enteric dabigatran administration. Liposomes achieved reversal of TCT to baseline at low levels of thrombin inhibition, and partial reversal of TCT at higher levels. Liposomes completely reversed the ef...","internal_url":"https://www.academia.edu/111277040/Reversal_of_lipophilic_weak_bases_using_pH_gradient_acidic_centre_liposomes_demonstration_of_effect_in_dabigatran_induced_anticoagulation","translated_internal_url":"","created_at":"2023-12-12T16:46:08.446-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Reversal_of_lipophilic_weak_bases_using_pH_gradient_acidic_centre_liposomes_demonstration_of_effect_in_dabigatran_induced_anticoagulation","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":61099,"name":"Thrombin","url":"https://www.academia.edu/Documents/in/Thrombin"},{"id":115194,"name":"Clinical Toxicology","url":"https://www.academia.edu/Documents/in/Clinical_Toxicology"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":189424,"name":"Blood Coagulation","url":"https://www.academia.edu/Documents/in/Blood_Coagulation"},{"id":189949,"name":"Anticoagulants","url":"https://www.academia.edu/Documents/in/Anticoagulants"},{"id":302037,"name":"In Vivo","url":"https://www.academia.edu/Documents/in/In_Vivo"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":413195,"name":"Time Factors","url":"https://www.academia.edu/Documents/in/Time_Factors"},{"id":482750,"name":"Dabigatran","url":"https://www.academia.edu/Documents/in/Dabigatran"},{"id":788677,"name":"Rabbits","url":"https://www.academia.edu/Documents/in/Rabbits"},{"id":1004785,"name":"Hemorrhage","url":"https://www.academia.edu/Documents/in/Hemorrhage"},{"id":1137254,"name":"Hydrogen-Ion Concentration","url":"https://www.academia.edu/Documents/in/Hydrogen-Ion_Concentration"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277038"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277038/Niosomes_and_discomes_for_ocular_delivery_of_naltrexone_hydrochloride_Morphological_rheological_spreading_properties_and_photo_protective_effects"><img alt="Research paper thumbnail of Niosomes and discomes for ocular delivery of naltrexone hydrochloride: Morphological, rheological, spreading properties and photo-protective effects" class="work-thumbnail" src="https://attachments.academia-assets.com/108858284/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277038/Niosomes_and_discomes_for_ocular_delivery_of_naltrexone_hydrochloride_Morphological_rheological_spreading_properties_and_photo_protective_effects">Niosomes and discomes for ocular delivery of naltrexone hydrochloride: Morphological, rheological, spreading properties and photo-protective effects</a></div><div class="wp-workCard_item"><span>International Journal of Pharmaceutics</span><span>, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5216a7c8a1a3aef5e9548ac3daea6c5d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858284,&quot;asset_id&quot;:111277038,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858284/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277038"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277038"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277038; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277038]").text(description); $(".js-view-count[data-work-id=111277038]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277038; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277038']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277038, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5216a7c8a1a3aef5e9548ac3daea6c5d" } } $('.js-work-strip[data-work-id=111277038]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277038,"title":"Niosomes and discomes for ocular delivery of naltrexone hydrochloride: Morphological, rheological, spreading properties and photo-protective effects","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"Naltrexone hydrochloride (NTX) is a promising treatment for corneal disorders linked to diabetes mellitus (diabetic keratopathy). However, NTX has a major stability problem due to autoxidation, which is likely to hinder its formulation as eye drops for treatment of diabetic keratopathy. In this study, in-house developed NTX non-ionic surfactant vesicles (niosomes and discomes) were evaluated for their spreading, rheological properties and their ability to impede the inevitable autoxidation of NTX in aqueous solutions. The measured contact angles and spreading coefficients for niosomes reflected significantly (P \u003c 0.05) better wetting and spreading abilities than the aqueous vehicle. The prepared niosomes were significantly more viscous (P \u003c 0.05) than the aqueous solution. The lipid content, size and composition of niosomes are the main factors affecting the viscosity of niosomal dispersions. Exposure of NTX solution to artificial daylight illumination (10,000 lux) can produce extensive degradation of NTX due to oxidation. The prepared formulations were able to significantly (P \u003c 0.05) protect the encapsulated NTX from the photo-induced oxidation compared with free NTX solutions. The investigated niosomes lend themselves as a potential ocular delivery modality for NTX.","publication_date":{"day":null,"month":null,"year":2012,"errors":{}},"publication_name":"International Journal of 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pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980419,"url":"https://api.elsevier.com/content/article/PII:S0378517312004681?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277036"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277036/In_situ_phase_transition_from_microemulsion_to_liquid_crystal_with_the_potential_of_prolonged_parenteral_drug_delivery"><img alt="Research paper thumbnail of In-situ phase transition from microemulsion to liquid crystal with the potential of prolonged parenteral drug delivery" class="work-thumbnail" src="https://attachments.academia-assets.com/108858287/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277036/In_situ_phase_transition_from_microemulsion_to_liquid_crystal_with_the_potential_of_prolonged_parenteral_drug_delivery">In-situ phase transition from microemulsion to liquid crystal with the potential of prolonged parenteral drug delivery</a></div><div class="wp-workCard_item"><span>International Journal of Pharmaceutics</span><span>, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="e62ddef1db2d06654be3aa34622961d4" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" 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window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277036]").text(description); $(".js-view-count[data-work-id=111277036]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277036; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277036']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277036, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "e62ddef1db2d06654be3aa34622961d4" } } $('.js-work-strip[data-work-id=111277036]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277036,"title":"In-situ phase transition from microemulsion to liquid crystal with the potential of prolonged parenteral drug delivery","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"This study is the first to investigate and demonstrate the potential of microemulsions (MEs) for sustained release parenteral drug delivery, due to phase transition behavior in aqueous environments. Phase diagrams were constructed with Miglyol 812N oil and a blend of (co)surfactants Solutol HS 15 and Span 80 with ethanol. Liquid crystal (LC) and coarse emulsion (CE) regions were found adjacent to the ME region in the water-rich corner of the phase diagram. Two formulations were selected, a LC-forming ME and a CE-forming ME and each were investigated with respect to their rheology, particle size, drug release profiles and particularly, the phase transition behavior. The spreadability in an aqueous environment was determined and release profiles from MEs were generated with gamma-scintigraphy. The CE-forming ME dispersed readily in an aqueous environment, whereas the LC-forming ME remained in a contracted region possibly due to the transition of ME to LC at the water/ME interface. Gamma-scintigraphy showed that the LC-forming ME had minimal spreadability and a slow release of 99m Tc in the first-order manner, suggesting phase conversion at the interface. In conclusion, owing to the potential of phase transition, LCforming MEs could be used as extravascular injectable drug delivery vehicles for prolonged drug release.","publication_date":{"day":null,"month":null,"year":2012,"errors":{}},"publication_name":"International Journal of 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sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980416,"url":"https://api.elsevier.com/content/article/PII:S0378517312003663?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277033"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277033/Absorption_and_tissue_tolerance_of_ricobendazole_in_the_presence_of_hydroxypropyl_%CE%B2_cyclodextrin_following_subcutaneous_injection_in_sheep"><img alt="Research paper thumbnail of Absorption and tissue tolerance of ricobendazole in the presence of hydroxypropyl-β-cyclodextrin following subcutaneous injection in sheep" class="work-thumbnail" src="https://attachments.academia-assets.com/108858254/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277033/Absorption_and_tissue_tolerance_of_ricobendazole_in_the_presence_of_hydroxypropyl_%CE%B2_cyclodextrin_following_subcutaneous_injection_in_sheep">Absorption and tissue tolerance of ricobendazole in the presence of hydroxypropyl-β-cyclodextrin following subcutaneous injection in sheep</a></div><div class="wp-workCard_item"><span>International Journal of Pharmaceutics</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="41219d67105f437ffc70337b201ba4e5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858254,&quot;asset_id&quot;:111277033,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858254/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277033"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277033"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277033; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277033]").text(description); $(".js-view-count[data-work-id=111277033]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277033; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277033']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277033, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "41219d67105f437ffc70337b201ba4e5" } } $('.js-work-strip[data-work-id=111277033]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277033,"title":"Absorption and tissue tolerance of ricobendazole in the presence of hydroxypropyl-β-cyclodextrin following subcutaneous injection in sheep","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"Post-injection precipitation may cause poor and erratic drug absorption and tissue irritation at the injection site. Tissue tolerance and pharmacokinetics of a low pH ricobendazole (RBZ) injectable containing 20% hydroxypropyl-␤-cyclodextrin (HP-␤-CD) were simultaneously investigated after subcutaneous injection in sheep compared to a reference formulation without HP-␤-CD. Each animal received a RBZ containing formulation on one side of the back and the respective vehicle on the contralateral side. The HP-␤-CD vehicle showed good tissue tolerance and the acidic solution caused minimal injection site reactions. Both RBZ containing formulations caused pain on injection and tissue histological changes in some animals. Lack of elevation of plasma creatine kinase indicated that none of the formulations caused significant damage to the underlying muscle tissue. Compared to the reference formulation, AUC and C max of the HP-␤-CD formulation were 1.6 and 2.2 times higher, respectively, whereas t max , MRT and t 1/2 were significantly shorter suggesting faster and greater absorption of RBZ in the presence of HP-␤-CD. This was attributed to the effect of inhibition of post-injection drug precipitation and drug absorption enhancement of HP-␤-CD. In conclusion, HP-␤-CD was shown to be a tissue-compatible excipient with potential to inhibit post-injection precipitation and increase absorption of poorly water soluble drugs. Additionally, the HP-␤-CD formulation showed promise as an injectable that potentially minimizes irritation by reducing the dose required.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"International Journal of 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$a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277031"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277031/Conjunctival_and_corneal_tolerability_assessment_of_ocular_naltrexone_niosomes_and_their_ingredients_on_the_hens_egg_chorioallantoic_membrane_and_excised_bovine_cornea_models"><img alt="Research paper thumbnail of Conjunctival and corneal tolerability assessment of ocular naltrexone niosomes and their ingredients on the hen&#39;s egg chorioallantoic membrane and excised bovine cornea models" class="work-thumbnail" src="https://attachments.academia-assets.com/108858253/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277031/Conjunctival_and_corneal_tolerability_assessment_of_ocular_naltrexone_niosomes_and_their_ingredients_on_the_hens_egg_chorioallantoic_membrane_and_excised_bovine_cornea_models">Conjunctival and corneal tolerability assessment of ocular naltrexone niosomes and their ingredients on the hen&#39;s egg chorioallantoic membrane and excised bovine cornea models</a></div><div class="wp-workCard_item"><span>International Journal of Pharmaceutics</span><span>, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="beeb697a2b6f1eba21df2b7f85b30523" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858253,&quot;asset_id&quot;:111277031,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" 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test-chorioallantoic membrane (HET-CAM), bovine corneal opacity and permeability (BCOP) test and histological examination of excised corneas to evaluate the conjunctival and corneal toxicity of niosomes and their ingredients. Various surfactant/lipid combinations and concentrations (1-10%, w/v) were investigated for the ocular delivery of an ambitious drug (naltrexone hydrochloride) for treatment of diabetic keratopathy. Four niosomal formulations were investigated and found to be non irritant to the 10 days old HET-CAMs (an acceptable conjunctival model). Only one of the tested ingredients (sodium cholate-CH) showed moderate irritation, however such an effect was diminished when incorporated into niosomes. Corneal opacity and fluorescein permeability scores for the test substances correlated well with the HET-CAM test results. Corneal erosion and stromal thickness were found to be in agreement with the HET-CAM and BCOP results, which discriminated well between moderately and mildly irritant test substances. Corneal histological examination revealed toxicity signs included epithelial erosion, stromal condensation and stromal vacuolisation, which allowed better discrimination between strong and moderate irritants. It is concluded that the prepared niosomes possess good ocular tolerability and minimal ocular tissue irritation. They can be further investigated as ocular delivery systems using appropriate animal models.","publication_date":{"day":null,"month":null,"year":2012,"errors":{}},"publication_name":"International Journal of 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Opacity","url":"https://www.academia.edu/Documents/in/Corneal_Opacity"},{"id":402759,"name":"Chickens","url":"https://www.academia.edu/Documents/in/Chickens"},{"id":767931,"name":"Naltrexone","url":"https://www.academia.edu/Documents/in/Naltrexone"},{"id":1384707,"name":"Niosomes","url":"https://www.academia.edu/Documents/in/Niosomes"},{"id":2534790,"name":"Chorioallantoic Membrane","url":"https://www.academia.edu/Documents/in/Chorioallantoic_Membrane"},{"id":2641150,"name":"Tolerability","url":"https://www.academia.edu/Documents/in/Tolerability"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":3881526,"name":"In Vitro Techniques","url":"https://www.academia.edu/Documents/in/In_Vitro_Techniques"}],"urls":[{"id":36980412,"url":"https://api.elsevier.com/content/article/PII:S0378517312004097?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277029"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277029/In_vitro_prediction_of_bioavailability_following_extravascular_injection_of_poorly_soluble_drugs_an_insight_into_clinical_failure_and_the_role_of_delivery_systems"><img alt="Research paper thumbnail of In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems" class="work-thumbnail" src="https://attachments.academia-assets.com/108858216/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277029/In_vitro_prediction_of_bioavailability_following_extravascular_injection_of_poorly_soluble_drugs_an_insight_into_clinical_failure_and_the_role_of_delivery_systems">In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems</a></div><div class="wp-workCard_item"><span>Journal of Pharmacy and Pharmacology</span><span>, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Objectives To investigate the feasibility of using an in-vitro model to simulate the incidence of...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Objectives To investigate the feasibility of using an in-vitro model to simulate the incidence of post-injection drug precipitation (PDP), and to identify the roles of drug properties and delivery systems in its occurrence. Methods A literature review on incomplete absorption following extravascular injection (subcutaneous and intramuscular) was conducted. Six model drugs in nine different formulations were studied for an in-vitro/in-vivo correlation. A rapid in-vitro dilution method using a 96-well plate was used for predicting PDP by dilution with a physiological buffer. New formulations based on hydroxypropyl-β-cyclodextrin (CD), with and without co-solvents or pH control, were developed and tested on the in-vitro model. Key findings The occurrence of precipitation detected from the in-vitro dilution model appeared to be correlated with clinical reports and animal studies. The formulation components played an important role in determining the potential for drug precipitation on d...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ddb26841f330c37f5c2ef4c966a049b2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858216,&quot;asset_id&quot;:111277029,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858216/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277029"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277029"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277029; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277029]").text(description); $(".js-view-count[data-work-id=111277029]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277029; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277029']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277029, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ddb26841f330c37f5c2ef4c966a049b2" } } $('.js-work-strip[data-work-id=111277029]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277029,"title":"In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems","translated_title":"","metadata":{"abstract":"Objectives To investigate the feasibility of using an in-vitro model to simulate the incidence of post-injection drug precipitation (PDP), and to identify the roles of drug properties and delivery systems in its occurrence. Methods A literature review on incomplete absorption following extravascular injection (subcutaneous and intramuscular) was conducted. Six model drugs in nine different formulations were studied for an in-vitro/in-vivo correlation. A rapid in-vitro dilution method using a 96-well plate was used for predicting PDP by dilution with a physiological buffer. New formulations based on hydroxypropyl-β-cyclodextrin (CD), with and without co-solvents or pH control, were developed and tested on the in-vitro model. Key findings The occurrence of precipitation detected from the in-vitro dilution model appeared to be correlated with clinical reports and animal studies. 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data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277026/Physicochemical_Characterization_of_Ricobendazole_I_Solubility_Lipophilicity_and_Ionization_Characteristics"><img alt="Research paper thumbnail of Physicochemical Characterization of Ricobendazole: I. Solubility, Lipophilicity, and Ionization Characteristics" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277026/Physicochemical_Characterization_of_Ricobendazole_I_Solubility_Lipophilicity_and_Ionization_Characteristics">Physicochemical Characterization of Ricobendazole: I. Solubility, Lipophilicity, and Ionization Characteristics</a></div><div class="wp-workCard_item"><span>Journal of Pharmaceutical Sciences</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The physicochemical properties of ricobendazole (RBZ) were characterized using conventional metho...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The physicochemical properties of ricobendazole (RBZ) were characterized using conventional methods. Solubility in some pharmaceutical solvents, pH-solubility, ionization properties, and lipophilicity are described. The solubility of RBZ in water is 62 mug/mL and very poor in common pharmaceutical solvents, for example, oils (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.25 mg/mL in all the tested oils) or ethanol (1.2 mg/mL) and propylene glycol (2.6 mg/mL), and slightly higher in dipolar solvents, DMSO (16.5 mg/mL). U-shaped pH-solubility profile in aqueous solutions indicates RBZ is an ampholyte. pK(a) values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 for the basic group and 9.82 and 9.53 for the non-basic nitrogen, respectively. Combination of low pH and surfactant/co-solvent mixtures also improved solubility. RBZ formed a 1:1 complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a binding constant (K(1:1)) of 311/M1. Apparent partition coefficients of RBZ were 14.3-15.2 at pH 6-9 and reduced at higher or lower pH. In conclusion, traditional organic co-solvents, pH-adjustment or complexation (with HP-beta-CD) approaches are unlikely to yield sufficient solubility for formulation of RBZ solutions for subcutaneous injection and novel approaches should be considered.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277026"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277026"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277026; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277026]").text(description); $(".js-view-count[data-work-id=111277026]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277026; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277026']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277026, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277026]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277026,"title":"Physicochemical Characterization of Ricobendazole: I. Solubility, Lipophilicity, and Ionization Characteristics","translated_title":"","metadata":{"abstract":"The physicochemical properties of ricobendazole (RBZ) were characterized using conventional methods. Solubility in some pharmaceutical solvents, pH-solubility, ionization properties, and lipophilicity are described. The solubility of RBZ in water is 62 mug/mL and very poor in common pharmaceutical solvents, for example, oils (\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.25 mg/mL in all the tested oils) or ethanol (1.2 mg/mL) and propylene glycol (2.6 mg/mL), and slightly higher in dipolar solvents, DMSO (16.5 mg/mL). U-shaped pH-solubility profile in aqueous solutions indicates RBZ is an ampholyte. pK(a) values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 for the basic group and 9.82 and 9.53 for the non-basic nitrogen, respectively. Combination of low pH and surfactant/co-solvent mixtures also improved solubility. RBZ formed a 1:1 complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a binding constant (K(1:1)) of 311/M1. Apparent partition coefficients of RBZ were 14.3-15.2 at pH 6-9 and reduced at higher or lower pH. In conclusion, traditional organic co-solvents, pH-adjustment or complexation (with HP-beta-CD) approaches are unlikely to yield sufficient solubility for formulation of RBZ solutions for subcutaneous injection and novel approaches should be considered.","publisher":"Elsevier BV","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Journal of Pharmaceutical Sciences"},"translated_abstract":"The physicochemical properties of ricobendazole (RBZ) were characterized using conventional methods. Solubility in some pharmaceutical solvents, pH-solubility, ionization properties, and lipophilicity are described. The solubility of RBZ in water is 62 mug/mL and very poor in common pharmaceutical solvents, for example, oils (\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.25 mg/mL in all the tested oils) or ethanol (1.2 mg/mL) and propylene glycol (2.6 mg/mL), and slightly higher in dipolar solvents, DMSO (16.5 mg/mL). U-shaped pH-solubility profile in aqueous solutions indicates RBZ is an ampholyte. pK(a) values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 for the basic group and 9.82 and 9.53 for the non-basic nitrogen, respectively. Combination of low pH and surfactant/co-solvent mixtures also improved solubility. RBZ formed a 1:1 complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a binding constant (K(1:1)) of 311/M1. Apparent partition coefficients of RBZ were 14.3-15.2 at pH 6-9 and reduced at higher or lower pH. In conclusion, traditional organic co-solvents, pH-adjustment or complexation (with HP-beta-CD) approaches are unlikely to yield sufficient solubility for formulation of RBZ solutions for subcutaneous injection and novel approaches should be considered.","internal_url":"https://www.academia.edu/111277026/Physicochemical_Characterization_of_Ricobendazole_I_Solubility_Lipophilicity_and_Ionization_Characteristics","translated_internal_url":"","created_at":"2023-12-12T16:46:03.833-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Physicochemical_Characterization_of_Ricobendazole_I_Solubility_Lipophilicity_and_Ionization_Characteristics","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":428,"name":"Algorithms","url":"https://www.academia.edu/Documents/in/Algorithms"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":532,"name":"Physical Chemistry","url":"https://www.academia.edu/Documents/in/Physical_Chemistry"},{"id":23390,"name":"Pharmaceutical Chemistry","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Chemistry"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":52055,"name":"Lipids","url":"https://www.academia.edu/Documents/in/Lipids"},{"id":89956,"name":"Pharmaceutical Sciences","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Sciences"},{"id":205584,"name":"Solubility","url":"https://www.academia.edu/Documents/in/Solubility"},{"id":206307,"name":"Albendazole","url":"https://www.academia.edu/Documents/in/Albendazole"},{"id":246560,"name":"High Pressure Liquid Chromatography","url":"https://www.academia.edu/Documents/in/High_Pressure_Liquid_Chromatography"},{"id":329196,"name":"Ionization","url":"https://www.academia.edu/Documents/in/Ionization"},{"id":498676,"name":"Lipophilicity","url":"https://www.academia.edu/Documents/in/Lipophilicity"},{"id":756431,"name":"log P","url":"https://www.academia.edu/Documents/in/log_P"},{"id":989646,"name":"Aqueous Solution","url":"https://www.academia.edu/Documents/in/Aqueous_Solution"},{"id":1137254,"name":"Hydrogen-Ion Concentration","url":"https://www.academia.edu/Documents/in/Hydrogen-Ion_Concentration"},{"id":1186482,"name":"Solvent","url":"https://www.academia.edu/Documents/in/Solvent"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980407,"url":"https://api.elsevier.com/content/article/PII:S0022354916317701?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277024"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277024/Synthesis_and_pharmacokinetics_of_strontium_fructose_1_6_diphosphate_Sr_FDP_as_a_potential_anti_osteoporosis_agent_in_intact_and_ovariectomized_rats"><img alt="Research paper thumbnail of Synthesis and pharmacokinetics of strontium fructose 1,6-diphosphate (Sr-FDP) as a potential anti-osteoporosis agent in intact and ovariectomized rats" class="work-thumbnail" src="https://attachments.academia-assets.com/108858250/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277024/Synthesis_and_pharmacokinetics_of_strontium_fructose_1_6_diphosphate_Sr_FDP_as_a_potential_anti_osteoporosis_agent_in_intact_and_ovariectomized_rats">Synthesis and pharmacokinetics of strontium fructose 1,6-diphosphate (Sr-FDP) as a potential anti-osteoporosis agent in intact and ovariectomized rats</a></div><div class="wp-workCard_item"><span>Journal of Inorganic Biochemistry</span><span>, 2011</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dd18718fd4036dad7e51035128b09d6c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858250,&quot;asset_id&quot;:111277024,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858250/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277024"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277024"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277024; 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The compound was characterized and confirmed with elemental analyses and spectroscopic (IR, NMR) methods. The pharmacokinetic profiles of Sr-FDP were investigated in Sprague-Dawley rats following oral administration at a dose of 110, 220, and 440 mg/kg respectively. Pharmacokinetic differences were also compared in intact rats and ovariectomized rats with and without estrogen supplement. Strontium concentrations in plasma, urine, tissue and feces were determined by graphite furnace atomic absorption spectroscopy (GFAAS). The results showed that Sr-FDP was absorbed rapidly with T max b 1 h in all the groups with AUC 0-∞ proportional to the oral dose. The pharmacokinetic profiles were characterized by long half-life, a large apparent volume of distribution. The highest Sr concentration was observed in the bone at 6 h, and the level of Sr decreased close to the baseline in heart, liver, spleen, lung, intestine, brain and kidney after 12 h. The cumulative amounts of Sr over 96 h were found to be~3% in urine, but~70% in feces suggesting that the parent drug was mainly excreted from the intestine. The C max and AUC 0-∞ of Sr-FDP in ovariectomized rats were significantly decreased compared to those in intact rats, and this trend was ameliorated by using 17-beta-estradiol (E 2) treatment in the ovariectomized rats.","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Journal of Inorganic Biochemistry","grobid_abstract_attachment_id":108858250},"translated_abstract":null,"internal_url":"https://www.academia.edu/111277024/Synthesis_and_pharmacokinetics_of_strontium_fructose_1_6_diphosphate_Sr_FDP_as_a_potential_anti_osteoporosis_agent_in_intact_and_ovariectomized_rats","translated_internal_url":"","created_at":"2023-12-12T16:46:02.952-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858250,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858250/thumbnails/1.jpg","file_name":"j.jinorgbio.2011.01.00120231213-1-tund90.pdf","download_url":"https://www.academia.edu/attachments/108858250/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Synthesis_and_pharmacokinetics_of_stront.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858250/j.jinorgbio.2011.01.00120231213-1-tund90-libre.pdf?1702428623=\u0026response-content-disposition=attachment%3B+filename%3DSynthesis_and_pharmacokinetics_of_stront.pdf\u0026Expires=1732823520\u0026Signature=R~mGAKRJ41MtyzN-08~z7KMCLJ4BSNH3GBlCDmGxCebqOWB6fqjfpF4Tl-vJex~XTP0MF8oAGr1XbnFWlvgGbkqRyVs22Xd~182cszHmNKoTF5JWzNigBdeFMD4coabcVLt1jXH3-NfuqQvfWE65jUgTx86xtpbdDG9f~pvOnxKTHvHRWBxHu7zVDgHV0TqTyrMCMjP698kGDLR7l~UDjN-HsYi0isX80JHEPOEe302JVgR6cmHljxPCqgW0~5Mo6y3HSVCluvv7cddtb2Rbu5pQuCk4~DhiHbep5cI~nyTPJwt3PHejxZ1VpJotb7ZPxwolFG6NU-~AK-Z7APxAQg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Synthesis_and_pharmacokinetics_of_strontium_fructose_1_6_diphosphate_Sr_FDP_as_a_potential_anti_osteoporosis_agent_in_intact_and_ovariectomized_rats","translated_slug":"","page_count":6,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858250,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858250/thumbnails/1.jpg","file_name":"j.jinorgbio.2011.01.00120231213-1-tund90.pdf","download_url":"https://www.academia.edu/attachments/108858250/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Synthesis_and_pharmacokinetics_of_stront.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858250/j.jinorgbio.2011.01.00120231213-1-tund90-libre.pdf?1702428623=\u0026response-content-disposition=attachment%3B+filename%3DSynthesis_and_pharmacokinetics_of_stront.pdf\u0026Expires=1732823520\u0026Signature=R~mGAKRJ41MtyzN-08~z7KMCLJ4BSNH3GBlCDmGxCebqOWB6fqjfpF4Tl-vJex~XTP0MF8oAGr1XbnFWlvgGbkqRyVs22Xd~182cszHmNKoTF5JWzNigBdeFMD4coabcVLt1jXH3-NfuqQvfWE65jUgTx86xtpbdDG9f~pvOnxKTHvHRWBxHu7zVDgHV0TqTyrMCMjP698kGDLR7l~UDjN-HsYi0isX80JHEPOEe302JVgR6cmHljxPCqgW0~5Mo6y3HSVCluvv7cddtb2Rbu5pQuCk4~DhiHbep5cI~nyTPJwt3PHejxZ1VpJotb7ZPxwolFG6NU-~AK-Z7APxAQg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":154,"name":"Endocrinology","url":"https://www.academia.edu/Documents/in/Endocrinology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":530,"name":"Inorganic Chemistry","url":"https://www.academia.edu/Documents/in/Inorganic_Chemistry"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":63997,"name":"Osteoporosis","url":"https://www.academia.edu/Documents/in/Osteoporosis"},{"id":65390,"name":"Internal Medicine","url":"https://www.academia.edu/Documents/in/Internal_Medicine"},{"id":78130,"name":"Strontium","url":"https://www.academia.edu/Documents/in/Strontium"},{"id":178360,"name":"Urine","url":"https://www.academia.edu/Documents/in/Urine"},{"id":235677,"name":"Behavioral Animal Models","url":"https://www.academia.edu/Documents/in/Behavioral_Animal_Models"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":702312,"name":"Atomic Absorption Spectroscopy","url":"https://www.academia.edu/Documents/in/Atomic_Absorption_Spectroscopy"},{"id":773664,"name":"Inorganic Biochemistry","url":"https://www.academia.edu/Documents/in/Inorganic_Biochemistry"},{"id":1993786,"name":"Cumulant","url":"https://www.academia.edu/Documents/in/Cumulant"},{"id":2053987,"name":"Ovariectomy","url":"https://www.academia.edu/Documents/in/Ovariectomy"},{"id":2229160,"name":"Ovariectomized Rat","url":"https://www.academia.edu/Documents/in/Ovariectomized_Rat"},{"id":2950651,"name":"Tissue distribution","url":"https://www.academia.edu/Documents/in/Tissue_distribution"}],"urls":[{"id":36980405,"url":"https://api.elsevier.com/content/article/PII:S016201341100002X?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277022"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277022/Pre_formulation_and_chemical_stability_studies_of_penethamate_a_benzylpenicillin_ester_prodrug_in_aqueous_vehicles"><img alt="Research paper thumbnail of Pre-formulation and chemical stability studies of penethamate, a benzylpenicillin ester prodrug, in aqueous vehicles" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277022/Pre_formulation_and_chemical_stability_studies_of_penethamate_a_benzylpenicillin_ester_prodrug_in_aqueous_vehicles">Pre-formulation and chemical stability studies of penethamate, a benzylpenicillin ester prodrug, in aqueous vehicles</a></div><div class="wp-workCard_item"><span>Drug Development and Industrial Pharmacy</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine m...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277022"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277022"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277022; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277022]").text(description); $(".js-view-count[data-work-id=111277022]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277022; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277022']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277022, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277022]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277022,"title":"Pre-formulation and chemical stability studies of penethamate, a benzylpenicillin ester prodrug, in aqueous vehicles","translated_title":"","metadata":{"abstract":"Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.","publisher":"Informa UK Limited","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Drug Development and Industrial Pharmacy"},"translated_abstract":"Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.","internal_url":"https://www.academia.edu/111277022/Pre_formulation_and_chemical_stability_studies_of_penethamate_a_benzylpenicillin_ester_prodrug_in_aqueous_vehicles","translated_internal_url":"","created_at":"2023-12-12T16:46:02.335-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Pre_formulation_and_chemical_stability_studies_of_penethamate_a_benzylpenicillin_ester_prodrug_in_aqueous_vehicles","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":2215,"name":"Water","url":"https://www.academia.edu/Documents/in/Water"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":13841,"name":"Drug development","url":"https://www.academia.edu/Documents/in/Drug_development"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":64461,"name":"Prodrugs","url":"https://www.academia.edu/Documents/in/Prodrugs"},{"id":133177,"name":"Temperature","url":"https://www.academia.edu/Documents/in/Temperature"},{"id":178352,"name":"Prodrug","url":"https://www.academia.edu/Documents/in/Prodrug"},{"id":205584,"name":"Solubility","url":"https://www.academia.edu/Documents/in/Solubility"},{"id":207059,"name":"Suspensions","url":"https://www.academia.edu/Documents/in/Suspensions"},{"id":376308,"name":"Buffers","url":"https://www.academia.edu/Documents/in/Buffers"},{"id":414692,"name":"Solutions","url":"https://www.academia.edu/Documents/in/Solutions"},{"id":989646,"name":"Aqueous Solution","url":"https://www.academia.edu/Documents/in/Aqueous_Solution"},{"id":1121353,"name":"Esters","url":"https://www.academia.edu/Documents/in/Esters"},{"id":1135766,"name":"Excipients","url":"https://www.academia.edu/Documents/in/Excipients"},{"id":1135814,"name":"Drug Stability","url":"https://www.academia.edu/Documents/in/Drug_Stability"},{"id":1186482,"name":"Solvent","url":"https://www.academia.edu/Documents/in/Solvent"},{"id":1745595,"name":"Solvents","url":"https://www.academia.edu/Documents/in/Solvents"},{"id":2298646,"name":"Penicillin G","url":"https://www.academia.edu/Documents/in/Penicillin_G"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980403,"url":"http://www.tandfonline.com/doi/pdf/10.3109/03639045.2011.590497"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277020"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277020/Gas_Chromatography_Time_Of_Flight_Mass_Spectrometry_Based_Metabolomic_Analysis_of_Human_Macrophages_Infected_byM_tuberculosis"><img alt="Research paper thumbnail of Gas Chromatography Time-Of-Flight Mass Spectrometry-Based Metabolomic Analysis of Human Macrophages Infected byM. tuberculosis" class="work-thumbnail" src="https://attachments.academia-assets.com/108858248/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277020/Gas_Chromatography_Time_Of_Flight_Mass_Spectrometry_Based_Metabolomic_Analysis_of_Human_Macrophages_Infected_byM_tuberculosis">Gas Chromatography Time-Of-Flight Mass Spectrometry-Based Metabolomic Analysis of Human Macrophages Infected byM. tuberculosis</a></div><div class="wp-workCard_item"><span>Analytical Letters</span><span>, 2013</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2f2a03c82eba5402e754a69ed593fbbd" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858248,&quot;asset_id&quot;:111277020,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858248/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277020"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277020"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277020; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277020]").text(description); $(".js-view-count[data-work-id=111277020]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277020; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277020']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277020, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "2f2a03c82eba5402e754a69ed593fbbd" } } $('.js-work-strip[data-work-id=111277020]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277020,"title":"Gas Chromatography Time-Of-Flight Mass Spectrometry-Based Metabolomic Analysis of Human Macrophages Infected byM. tuberculosis","translated_title":"","metadata":{"publisher":"Informa UK Limited","grobid_abstract":"In this study the spectrum storage rate, linearity of response, and detection limits of time-of-flight mass spectrometry in combination with capillary Ž. gas chromatography GC᎐TOF-MS were evaluated. TOF-MS was found to be a very powerful technique with limits of detection in the low pg range for Ž. Ž. organophosphorus pesticides OPPs, 1᎐6 pg , triazine herbicides 4᎐60 pg and Ž. polycyclic aromatic hydrocarbons 0.3᎐6 pg. Spectral information of good quality was obtained at spectrum storage rates of up to 500 Hz. For all analyte classes response concentration plots were linear in the range 2 pg᎐1 ng, which is very important in TOF-MS. GC᎐TOF-MS was applied to the determination of the above compound classes in various extracts, which were obtained by means of miniaturized extraction procedures. The analytes were extracted from aqueous Ž. samples surface water, tea and sediment into an organic solvent and 1 L of the extract was injected into the GC system using a split injector. One software tool, automated spectral peak deconvolution, turned out to be very valuable. It enabled calculation of spectra from overlapping peaks even if their retention times differed only three scans. Peaks were reported with their deconvoluted spectrum, the so-called peak true spectrum. In actual practice this means that peaks had to be separated for 0.3 or 0.15 s at a spectrum storage rate of 10 and 20 Hz, respectively. Three extraction procedures combined with GC᎐TOF-MS allowed the analysis of the microcontaminants at 0.1 grL in surface water, at 2 grL in tea, and at Ž. 0.01 mgrkg in sediment with a signal-to-noise ratio SrN of 10. In other words, relevant real-life detection limits can be obtained even under split injection conditions.","publication_date":{"day":null,"month":null,"year":2013,"errors":{}},"publication_name":"Analytical Letters","grobid_abstract_attachment_id":108858248},"translated_abstract":null,"internal_url":"https://www.academia.edu/111277020/Gas_Chromatography_Time_Of_Flight_Mass_Spectrometry_Based_Metabolomic_Analysis_of_Human_Macrophages_Infected_byM_tuberculosis","translated_internal_url":"","created_at":"2023-12-12T16:46:01.793-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858248,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858248/thumbnails/1.jpg","file_name":"28sici291520-667x2819991129113A93C6633A3Aaid-mcs43E3.0.co3B2-020231213-1-mfe7uo.pdf","download_url":"https://www.academia.edu/attachments/108858248/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Gas_Chromatography_Time_Of_Flight_Mass_S.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858248/28sici291520-667x2819991129113A93C6633A3Aaid-mcs43E3.0.co3B2-020231213-1-mfe7uo-libre.pdf?1702428625=\u0026response-content-disposition=attachment%3B+filename%3DGas_Chromatography_Time_Of_Flight_Mass_S.pdf\u0026Expires=1732823520\u0026Signature=bHs65ishhgbKDbYFxCnL91bvAYG-2dt4pBjZ21IMQK~XdE-MIPuKL89hGX6dEfslmBJQff7WrRvjc060JNV13qoGsBZBeSvFO3Q88vMSOlD3lSmFfsm4x3s4OhyHVSm7MXdSewpTjFAFNHpiC3sHcLVo0UHMhuddz8zWyVZPsseBmRrJ2MdSrjLOV~E-BJF3-I~9jqY1SJgYzrGptY07~Jk3-Cx0GTVjL~QyIYsYm-r-f33FKe7Chx6j2PSiWO63HSTNmjbZemhSvsJYCWWTgwACsU0Z5RXsmic5JlmKWvYqVo43INKxTwdWBcYb3PG6-RH~iNewjoZycX11WeSfuw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Gas_Chromatography_Time_Of_Flight_Mass_Spectrometry_Based_Metabolomic_Analysis_of_Human_Macrophages_Infected_byM_tuberculosis","translated_slug":"","page_count":13,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858248,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858248/thumbnails/1.jpg","file_name":"28sici291520-667x2819991129113A93C6633A3Aaid-mcs43E3.0.co3B2-020231213-1-mfe7uo.pdf","download_url":"https://www.academia.edu/attachments/108858248/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Gas_Chromatography_Time_Of_Flight_Mass_S.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858248/28sici291520-667x2819991129113A93C6633A3Aaid-mcs43E3.0.co3B2-020231213-1-mfe7uo-libre.pdf?1702428625=\u0026response-content-disposition=attachment%3B+filename%3DGas_Chromatography_Time_Of_Flight_Mass_S.pdf\u0026Expires=1732823520\u0026Signature=bHs65ishhgbKDbYFxCnL91bvAYG-2dt4pBjZ21IMQK~XdE-MIPuKL89hGX6dEfslmBJQff7WrRvjc060JNV13qoGsBZBeSvFO3Q88vMSOlD3lSmFfsm4x3s4OhyHVSm7MXdSewpTjFAFNHpiC3sHcLVo0UHMhuddz8zWyVZPsseBmRrJ2MdSrjLOV~E-BJF3-I~9jqY1SJgYzrGptY07~Jk3-Cx0GTVjL~QyIYsYm-r-f33FKe7Chx6j2PSiWO63HSTNmjbZemhSvsJYCWWTgwACsU0Z5RXsmic5JlmKWvYqVo43INKxTwdWBcYb3PG6-RH~iNewjoZycX11WeSfuw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":524,"name":"Analytical Chemistry","url":"https://www.academia.edu/Documents/in/Analytical_Chemistry"},{"id":4656,"name":"Chromatography","url":"https://www.academia.edu/Documents/in/Chromatography"},{"id":5769,"name":"Mass Spectrometry","url":"https://www.academia.edu/Documents/in/Mass_Spectrometry"},{"id":7802,"name":"Metabolomics","url":"https://www.academia.edu/Documents/in/Metabolomics"},{"id":9786,"name":"Proteomics","url":"https://www.academia.edu/Documents/in/Proteomics"},{"id":62235,"name":"Tuberculosis","url":"https://www.academia.edu/Documents/in/Tuberculosis"},{"id":68318,"name":"Mycobacterium tuberculosis","url":"https://www.academia.edu/Documents/in/Mycobacterium_tuberculosis"},{"id":764799,"name":"Metabolic pathway","url":"https://www.academia.edu/Documents/in/Metabolic_pathway"},{"id":1292327,"name":"Metabolome","url":"https://www.academia.edu/Documents/in/Metabolome"}],"urls":[{"id":36980401,"url":"http://www.tandfonline.com/doi/pdf/10.1080/00032719.2013.777924"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111276916"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111276916/Co_Delivery_Using_pH_Sensitive_Liposomes_to_Pancreatic_Cancer_Cells_the_Effects_of_Curcumin_on_Cellular_Concentration_and_Pharmacokinetics_of_Gemcitabine"><img alt="Research paper thumbnail of Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111276916/Co_Delivery_Using_pH_Sensitive_Liposomes_to_Pancreatic_Cancer_Cells_the_Effects_of_Curcumin_on_Cellular_Concentration_and_Pharmacokinetics_of_Gemcitabine">Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine</a></div><div class="wp-workCard_item"><span>Pharmaceutical Research</span><span>, Jun 29, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">PURPOSE PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were inv...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">PURPOSE PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were investigated for the potential application in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) treatment. Curcumin was employed as an inhibitor of the efflux transporter, multidrug resistance protein 5 (MRP5) in PDAC cells. METHODS Liposomes were prepared with gemcitabine in the core and curcumin in the bilayers. The effects of curcumin on pH-sensitivity and &amp;#39;endosome escape&amp;#39; of PSL with different PEGylation were investigated using a calcein self-quench assay. The effects of curcumin on intracellular gemcitabine concentrations, and cytotoxicity to a MIA PaCa-2 PDAC cell line was evaluated. The pharmacokinetics were investigated in rats following intravenous injection. RESULTS The addition of curcumin to the PSL bilayers (0.2-1 mol%)slightly decreased the pH-sensitivity of PSL, but to a less extent than PEGylation (0-5 mol%). Co-treatment with curcumin increased gemcitabine cellular accumulation in a concentration-dependent manner, and resulted in synergistic cytotoxicity towards MIA PaCa-2cells.Both these effects were augmented by the use of PSL, particularly when the two drugs were co-loaded in PSL. In rats, the dual-drug loaded PSL produced significantly reduced (p &amp;lt; 0.05) plasma clearance (CL) and volume of distribution (Vd) for both drugs, alongside 3 to 4-fold increases in the area-under-the-concentration-time curves compared to the free drugs. Additionally, curcumin slightly increase the plasma concentrations of gemcitabine possibly also via the MRP5 inhibition effect. CONCLUSION Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration thus cytotoxicity to MIA PaCa-2 cells but also significantly improved the pharmacokinetic profiles for both drugs. Graphical Abstract.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111276916"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111276916"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111276916; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111276916]").text(description); $(".js-view-count[data-work-id=111276916]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111276916; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111276916']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111276916, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111276916]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111276916,"title":"Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine","translated_title":"","metadata":{"abstract":"PURPOSE PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were investigated for the potential application in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) treatment. Curcumin was employed as an inhibitor of the efflux transporter, multidrug resistance protein 5 (MRP5) in PDAC cells. METHODS Liposomes were prepared with gemcitabine in the core and curcumin in the bilayers. The effects of curcumin on pH-sensitivity and \u0026#39;endosome escape\u0026#39; of PSL with different PEGylation were investigated using a calcein self-quench assay. The effects of curcumin on intracellular gemcitabine concentrations, and cytotoxicity to a MIA PaCa-2 PDAC cell line was evaluated. The pharmacokinetics were investigated in rats following intravenous injection. RESULTS The addition of curcumin to the PSL bilayers (0.2-1 mol%)slightly decreased the pH-sensitivity of PSL, but to a less extent than PEGylation (0-5 mol%). Co-treatment with curcumin increased gemcitabine cellular accumulation in a concentration-dependent manner, and resulted in synergistic cytotoxicity towards MIA PaCa-2cells.Both these effects were augmented by the use of PSL, particularly when the two drugs were co-loaded in PSL. In rats, the dual-drug loaded PSL produced significantly reduced (p \u0026lt; 0.05) plasma clearance (CL) and volume of distribution (Vd) for both drugs, alongside 3 to 4-fold increases in the area-under-the-concentration-time curves compared to the free drugs. Additionally, curcumin slightly increase the plasma concentrations of gemcitabine possibly also via the MRP5 inhibition effect. CONCLUSION Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration thus cytotoxicity to MIA PaCa-2 cells but also significantly improved the pharmacokinetic profiles for both drugs. Graphical Abstract.","publisher":"Springer Science+Business Media","publication_date":{"day":29,"month":6,"year":2021,"errors":{}},"publication_name":"Pharmaceutical Research"},"translated_abstract":"PURPOSE PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were investigated for the potential application in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) treatment. Curcumin was employed as an inhibitor of the efflux transporter, multidrug resistance protein 5 (MRP5) in PDAC cells. METHODS Liposomes were prepared with gemcitabine in the core and curcumin in the bilayers. The effects of curcumin on pH-sensitivity and \u0026#39;endosome escape\u0026#39; of PSL with different PEGylation were investigated using a calcein self-quench assay. The effects of curcumin on intracellular gemcitabine concentrations, and cytotoxicity to a MIA PaCa-2 PDAC cell line was evaluated. The pharmacokinetics were investigated in rats following intravenous injection. RESULTS The addition of curcumin to the PSL bilayers (0.2-1 mol%)slightly decreased the pH-sensitivity of PSL, but to a less extent than PEGylation (0-5 mol%). Co-treatment with curcumin increased gemcitabine cellular accumulation in a concentration-dependent manner, and resulted in synergistic cytotoxicity towards MIA PaCa-2cells.Both these effects were augmented by the use of PSL, particularly when the two drugs were co-loaded in PSL. In rats, the dual-drug loaded PSL produced significantly reduced (p \u0026lt; 0.05) plasma clearance (CL) and volume of distribution (Vd) for both drugs, alongside 3 to 4-fold increases in the area-under-the-concentration-time curves compared to the free drugs. Additionally, curcumin slightly increase the plasma concentrations of gemcitabine possibly also via the MRP5 inhibition effect. CONCLUSION Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration thus cytotoxicity to MIA PaCa-2 cells but also significantly improved the pharmacokinetic profiles for both drugs. Graphical Abstract.","internal_url":"https://www.academia.edu/111276916/Co_Delivery_Using_pH_Sensitive_Liposomes_to_Pancreatic_Cancer_Cells_the_Effects_of_Curcumin_on_Cellular_Concentration_and_Pharmacokinetics_of_Gemcitabine","translated_internal_url":"","created_at":"2023-12-12T16:44:14.199-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Co_Delivery_Using_pH_Sensitive_Liposomes_to_Pancreatic_Cancer_Cells_the_Effects_of_Curcumin_on_Cellular_Concentration_and_Pharmacokinetics_of_Gemcitabine","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":93232,"name":"Curcumin","url":"https://www.academia.edu/Documents/in/Curcumin"},{"id":95655,"name":"Pharmaceutical","url":"https://www.academia.edu/Documents/in/Pharmaceutical"},{"id":129181,"name":"PEGylation","url":"https://www.academia.edu/Documents/in/PEGylation"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980313,"url":"https://doi.org/10.1007/s11095-021-03072-2"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="105558650"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/105558650/Niosomal_Nanocarriers_for_Enhanced_Dermal_Delivery_of_Epigallocatechin_Gallate_for_Protection_against_Oxidative_Stress_of_the_Skin"><img alt="Research paper thumbnail of Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin" class="work-thumbnail" src="https://attachments.academia-assets.com/104978750/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/105558650/Niosomal_Nanocarriers_for_Enhanced_Dermal_Delivery_of_Epigallocatechin_Gallate_for_Protection_against_Oxidative_Stress_of_the_Skin">Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highe...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of −45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c884461427f53f3443dcbab5bab3a97d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:104978750,&quot;asset_id&quot;:105558650,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/104978750/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="105558650"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="105558650"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 105558650; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=105558650]").text(description); $(".js-view-count[data-work-id=105558650]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 105558650; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='105558650']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 105558650, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c884461427f53f3443dcbab5bab3a97d" } } $('.js-work-strip[data-work-id=105558650]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":105558650,"title":"Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin","translated_title":"","metadata":{"abstract":"Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of −45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival...","publisher":"MDPI AG","ai_title_tag":"Niosomal EGCG for Enhanced Skin Delivery and Antioxidant Protection","publication_name":"Pharmaceutics"},"translated_abstract":"Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="105558649"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/105558649/The_Preparation_of_High_content_Gemcitabine_pH_Sensitive_Liposomes_and_Evaluation_of_their_Cytotoxicity_to_Drug_Resistant_Pancreatic_Cancer_Cells"><img alt="Research paper thumbnail of The Preparation of High-content Gemcitabine pH Sensitive Liposomes and Evaluation of their Cytotoxicity to Drug Resistant Pancreatic Cancer Cells" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/105558649/The_Preparation_of_High_content_Gemcitabine_pH_Sensitive_Liposomes_and_Evaluation_of_their_Cytotoxicity_to_Drug_Resistant_Pancreatic_Cancer_Cells">The Preparation of High-content Gemcitabine pH Sensitive Liposomes and Evaluation of their Cytotoxicity to Drug Resistant Pancreatic Cancer Cells</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">SUMMARY Gemcitabine containing pH sensitive liposomes (PSL) has been prepared using a Small Volum...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">SUMMARY Gemcitabine containing pH sensitive liposomes (PSL) has been prepared using a Small Volume Incubation (SVI) method. The entrapment efficiency (EE) and drug loading (DL) were 29.5 ± 0.2% and 4.2 ± 0.2%, a respective 7and 70-fold increase compared to the thin film hydration extrusion (TFHE) method. The particle size and zeta potential were 146 ± 2 nm and -26.4 ± 2.0 mV. The gemcitabine PSL showed significantly enhanced cytotoxicity than free gemcitabine solution and gemcitabine non-pH-sensitive liposomes (NPSL) to pancreatic cancer cells. INTRODUCTION Over-expression of multidrug resistance proteins (MRP) in pancreatic cancer cells confers resistance to the major first-line drug, gemcitabine, due to MRP-mediated efflux of gemcitabine and/or its active metabolite[1]. This has posed a challenge in efficient intracellular delivery of gemcitabine to the nucleus of the cancer cells. The PSL, capable of endosomal escape after endocytosis, appear to be a suitable carrier system for d...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="105558649"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="105558649"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 105558649; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=105558649]").text(description); $(".js-view-count[data-work-id=105558649]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 105558649; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='105558649']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 105558649, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=105558649]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":105558649,"title":"The Preparation of High-content Gemcitabine pH Sensitive Liposomes and Evaluation of their Cytotoxicity to Drug Resistant Pancreatic Cancer Cells","translated_title":"","metadata":{"abstract":"SUMMARY Gemcitabine containing pH sensitive liposomes (PSL) has been prepared using a Small Volume Incubation (SVI) method. The entrapment efficiency (EE) and drug loading (DL) were 29.5 ± 0.2% and 4.2 ± 0.2%, a respective 7and 70-fold increase compared to the thin film hydration extrusion (TFHE) method. The particle size and zeta potential were 146 ± 2 nm and -26.4 ± 2.0 mV. The gemcitabine PSL showed significantly enhanced cytotoxicity than free gemcitabine solution and gemcitabine non-pH-sensitive liposomes (NPSL) to pancreatic cancer cells. INTRODUCTION Over-expression of multidrug resistance proteins (MRP) in pancreatic cancer cells confers resistance to the major first-line drug, gemcitabine, due to MRP-mediated efflux of gemcitabine and/or its active metabolite[1]. This has posed a challenge in efficient intracellular delivery of gemcitabine to the nucleus of the cancer cells. The PSL, capable of endosomal escape after endocytosis, appear to be a suitable carrier system for d...","publication_date":{"day":null,"month":null,"year":2014,"errors":{}}},"translated_abstract":"SUMMARY Gemcitabine containing pH sensitive liposomes (PSL) has been prepared using a Small Volume Incubation (SVI) method. The entrapment efficiency (EE) and drug loading (DL) were 29.5 ± 0.2% and 4.2 ± 0.2%, a respective 7and 70-fold increase compared to the thin film hydration extrusion (TFHE) method. The particle size and zeta potential were 146 ± 2 nm and -26.4 ± 2.0 mV. The gemcitabine PSL showed significantly enhanced cytotoxicity than free gemcitabine solution and gemcitabine non-pH-sensitive liposomes (NPSL) to pancreatic cancer cells. INTRODUCTION Over-expression of multidrug resistance proteins (MRP) in pancreatic cancer cells confers resistance to the major first-line drug, gemcitabine, due to MRP-mediated efflux of gemcitabine and/or its active metabolite[1]. This has posed a challenge in efficient intracellular delivery of gemcitabine to the nucleus of the cancer cells. The PSL, capable of endosomal escape after endocytosis, appear to be a suitable carrier system for d...","internal_url":"https://www.academia.edu/105558649/The_Preparation_of_High_content_Gemcitabine_pH_Sensitive_Liposomes_and_Evaluation_of_their_Cytotoxicity_to_Drug_Resistant_Pancreatic_Cancer_Cells","translated_internal_url":"","created_at":"2023-08-13T17:19:24.626-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"The_Preparation_of_High_content_Gemcitabine_pH_Sensitive_Liposomes_and_Evaluation_of_their_Cytotoxicity_to_Drug_Resistant_Pancreatic_Cancer_Cells","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26623,"name":"Pancreatic Cancer","url":"https://www.academia.edu/Documents/in/Pancreatic_Cancer"},{"id":42135,"name":"Drug","url":"https://www.academia.edu/Documents/in/Drug"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"}],"urls":[{"id":33405269,"url":"http://www.controlledreleasesociety.org/meetings/Documents/2014Abstracts/10391.pdf"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="5781428" id="papers"><div class="js-work-strip profile--work_container" data-work-id="115657199"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/115657199/Cyclic_RGDyC_functionalized_liposomes_for_dual_targeting_of_tumor_vasculature_and_cancer_cells_in_glioblastoma_An_in_vitro_boron_neutron_capture_therapy_study"><img alt="Research paper thumbnail of Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study" class="work-thumbnail" src="https://attachments.academia-assets.com/112003665/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/115657199/Cyclic_RGDyC_functionalized_liposomes_for_dual_targeting_of_tumor_vasculature_and_cancer_cells_in_glioblastoma_An_in_vitro_boron_neutron_capture_therapy_study">Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study</a></div><div class="wp-workCard_item"><span>Oncotarget</span><span>, 2017</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2eb598f4c72d88f01d6483e133ffb9e5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:112003665,&quot;asset_id&quot;:115657199,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/112003665/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="115657199"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="115657199"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 115657199; 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Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a αvβ3 ligand, cyclic arginine-glycine-aspartic acidtyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references. The results showed that both U87 and HUVEC had stronger expression of αvβ3 than other cell types, and the degree of cellular uptake of c(RGDyC)-LP correlated with the αvβ3-expression levels of the cells. In contrast, control liposomes without c(RGDyC) showed little cellular uptake, regardless of cell type. In an in vitro boron neutron capture therapy study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and significant lethal effects to both U87 and HUVEC than the control liposomes and drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different types of subsequent cell death. In conclusion, this study has demonstrated the potential of a new dual-targeting strategy using c(RGDyC)-LP to improve boron neutron capture therapy for glioblastoma.","publication_date":{"day":null,"month":null,"year":2017,"errors":{}},"publication_name":"Oncotarget","grobid_abstract_attachment_id":112003665},"translated_abstract":null,"internal_url":"https://www.academia.edu/115657199/Cyclic_RGDyC_functionalized_liposomes_for_dual_targeting_of_tumor_vasculature_and_cancer_cells_in_glioblastoma_An_in_vitro_boron_neutron_capture_therapy_study","translated_internal_url":"","created_at":"2024-03-01T20:14:38.726-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":112003665,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/112003665/thumbnails/1.jpg","file_name":"5bdcc3f536a4b0eb19d07a7186e64130b71e.pdf","download_url":"https://www.academia.edu/attachments/112003665/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Cyclic_RGDyC_functionalized_liposomes_fo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/112003665/5bdcc3f536a4b0eb19d07a7186e64130b71e-libre.pdf?1709354189=\u0026response-content-disposition=attachment%3B+filename%3DCyclic_RGDyC_functionalized_liposomes_fo.pdf\u0026Expires=1732823519\u0026Signature=L6xF~F3Xhjk3ZPkwLMHpTHEeOxNh6tw77kKl~3m7lNmggGl5tNtH0DvuTCdpnjyW5YcEiX-EtFg6vAjbCkBojUGK5IX1YhwFTGxkrjYK2RvU7JXsrXJ~hQTjQBQQtL0ZNbHyVBiijenRaxTBZAkaUK7OKV1NAiqPXBPFU40CT2Ci2Nsjkk-clTxoA3NW3CWf3ET1nICKvtgBG9H0r~6uuIvfAlNP2cqYSQc~96~bOR3xjtJc~BuBhUDaOXd9CcPhykOzZsEjjRQmymEeNqTY1wFyn2KcCpowNxymS4-SnVSbw7hmRXsc2qmjQkBJb9BTXvUxDNHwUzHeWakCBfSvRQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Cyclic_RGDyC_functionalized_liposomes_for_dual_targeting_of_tumor_vasculature_and_cancer_cells_in_glioblastoma_An_in_vitro_boron_neutron_capture_therapy_study","translated_slug":"","page_count":14,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":112003665,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/112003665/thumbnails/1.jpg","file_name":"5bdcc3f536a4b0eb19d07a7186e64130b71e.pdf","download_url":"https://www.academia.edu/attachments/112003665/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Cyclic_RGDyC_functionalized_liposomes_fo.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/112003665/5bdcc3f536a4b0eb19d07a7186e64130b71e-libre.pdf?1709354189=\u0026response-content-disposition=attachment%3B+filename%3DCyclic_RGDyC_functionalized_liposomes_fo.pdf\u0026Expires=1732823519\u0026Signature=L6xF~F3Xhjk3ZPkwLMHpTHEeOxNh6tw77kKl~3m7lNmggGl5tNtH0DvuTCdpnjyW5YcEiX-EtFg6vAjbCkBojUGK5IX1YhwFTGxkrjYK2RvU7JXsrXJ~hQTjQBQQtL0ZNbHyVBiijenRaxTBZAkaUK7OKV1NAiqPXBPFU40CT2Ci2Nsjkk-clTxoA3NW3CWf3ET1nICKvtgBG9H0r~6uuIvfAlNP2cqYSQc~96~bOR3xjtJc~BuBhUDaOXd9CcPhykOzZsEjjRQmymEeNqTY1wFyn2KcCpowNxymS4-SnVSbw7hmRXsc2qmjQkBJb9BTXvUxDNHwUzHeWakCBfSvRQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":22255,"name":"Cancer Research","url":"https://www.academia.edu/Documents/in/Cancer_Research"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":1190382,"name":"U","url":"https://www.academia.edu/Documents/in/U"}],"urls":[{"id":39949521,"url":"https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.16625"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277046"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277046/Development_of_Long_Circulating_pH_Sensitive_Liposomes_to_Circumvent_Gemcitabine_Resistance_in_Pancreatic_Cancer_Cells"><img alt="Research paper thumbnail of Development of Long-Circulating pH-Sensitive Liposomes to Circumvent Gemcitabine Resistance in Pancreatic Cancer Cells" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277046/Development_of_Long_Circulating_pH_Sensitive_Liposomes_to_Circumvent_Gemcitabine_Resistance_in_Pancreatic_Cancer_Cells">Development of Long-Circulating pH-Sensitive Liposomes to Circumvent Gemcitabine Resistance in Pancreatic Cancer Cells</a></div><div class="wp-workCard_item"><span>Pharmaceutical Research</span><span>, Mar 10, 2016</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investig...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investigate whether drug loading (DL) would alter the in vitro and pharmacokinetic properties. PSL with a high DL were obtained using a modified small-volume incubation method. The DL effects on drug release rate and in vitro cytotoxicity of PSL were evaluated using MIA PaCa-2 pancreatic cancer cells and their pharmacokinetics investigated in rats. The highest DL of 4.5 ± 0.1% was achieved for gemcitabine in PSL with 145 ± 5 nm diameter. DL did not alter the in vitro release rate from PSL. The IC50 (48 h) of PSL (DL 0.5 and 4.5%) and non pH-sensitive liposomes (NPSL, DL 4.2%) were 1.1 ± 0.1, 0.7 ± 0.1 and 37.0 ± 7.5 μM, respectively. The PSL resulted in a 4.2-fold increase in its elimination half-life (6.2 h) compared to gemcitabine solution (1.4 h) in rats. No significant difference in pharmacokinetic parameters was observed between the two PSL (DL 0.5 and 4.5%). The PSL offered advantages over NPSL in restoring the sensitivity of pancreatic cancer cells to gemcitabine without requiring a high DL. DL in the PSL did not alter release rate, cytotoxicity or their long-circulating properties. Graphical Abstract ᅟ.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277046"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277046"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277046; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277046]").text(description); $(".js-view-count[data-work-id=111277046]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277046; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277046']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277046, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277046]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277046,"title":"Development of Long-Circulating pH-Sensitive Liposomes to Circumvent Gemcitabine Resistance in Pancreatic Cancer Cells","translated_title":"","metadata":{"abstract":"To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investigate whether drug loading (DL) would alter the in vitro and pharmacokinetic properties. PSL with a high DL were obtained using a modified small-volume incubation method. The DL effects on drug release rate and in vitro cytotoxicity of PSL were evaluated using MIA PaCa-2 pancreatic cancer cells and their pharmacokinetics investigated in rats. The highest DL of 4.5 ± 0.1% was achieved for gemcitabine in PSL with 145 ± 5 nm diameter. DL did not alter the in vitro release rate from PSL. The IC50 (48 h) of PSL (DL 0.5 and 4.5%) and non pH-sensitive liposomes (NPSL, DL 4.2%) were 1.1 ± 0.1, 0.7 ± 0.1 and 37.0 ± 7.5 μM, respectively. The PSL resulted in a 4.2-fold increase in its elimination half-life (6.2 h) compared to gemcitabine solution (1.4 h) in rats. No significant difference in pharmacokinetic parameters was observed between the two PSL (DL 0.5 and 4.5%). The PSL offered advantages over NPSL in restoring the sensitivity of pancreatic cancer cells to gemcitabine without requiring a high DL. DL in the PSL did not alter release rate, cytotoxicity or their long-circulating properties. Graphical Abstract ᅟ.","publisher":"Springer Science+Business Media","publication_date":{"day":10,"month":3,"year":2016,"errors":{}},"publication_name":"Pharmaceutical Research"},"translated_abstract":"To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investigate whether drug loading (DL) would alter the in vitro and pharmacokinetic properties. PSL with a high DL were obtained using a modified small-volume incubation method. The DL effects on drug release rate and in vitro cytotoxicity of PSL were evaluated using MIA PaCa-2 pancreatic cancer cells and their pharmacokinetics investigated in rats. The highest DL of 4.5 ± 0.1% was achieved for gemcitabine in PSL with 145 ± 5 nm diameter. DL did not alter the in vitro release rate from PSL. The IC50 (48 h) of PSL (DL 0.5 and 4.5%) and non pH-sensitive liposomes (NPSL, DL 4.2%) were 1.1 ± 0.1, 0.7 ± 0.1 and 37.0 ± 7.5 μM, respectively. The PSL resulted in a 4.2-fold increase in its elimination half-life (6.2 h) compared to gemcitabine solution (1.4 h) in rats. No significant difference in pharmacokinetic parameters was observed between the two PSL (DL 0.5 and 4.5%). The PSL offered advantages over NPSL in restoring the sensitivity of pancreatic cancer cells to gemcitabine without requiring a high DL. DL in the PSL did not alter release rate, cytotoxicity or their long-circulating properties. Graphical Abstract ᅟ.","internal_url":"https://www.academia.edu/111277046/Development_of_Long_Circulating_pH_Sensitive_Liposomes_to_Circumvent_Gemcitabine_Resistance_in_Pancreatic_Cancer_Cells","translated_internal_url":"","created_at":"2023-12-12T16:46:10.086-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Development_of_Long_Circulating_pH_Sensitive_Liposomes_to_Circumvent_Gemcitabine_Resistance_in_Pancreatic_Cancer_Cells","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":26623,"name":"Pancreatic Cancer","url":"https://www.academia.edu/Documents/in/Pancreatic_Cancer"},{"id":59370,"name":"In Vitro","url":"https://www.academia.edu/Documents/in/In_Vitro"},{"id":92788,"name":"Pancreas","url":"https://www.academia.edu/Documents/in/Pancreas"},{"id":95655,"name":"Pharmaceutical","url":"https://www.academia.edu/Documents/in/Pharmaceutical"},{"id":138342,"name":"PSL","url":"https://www.academia.edu/Documents/in/PSL"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":390245,"name":"Particle Size","url":"https://www.academia.edu/Documents/in/Particle_Size"},{"id":1137254,"name":"Hydrogen-Ion Concentration","url":"https://www.academia.edu/Documents/in/Hydrogen-Ion_Concentration"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"},{"id":3521397,"name":"Pancreatic neoplasms","url":"https://www.academia.edu/Documents/in/Pancreatic_neoplasms"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":4132900,"name":"deoxycytidine ","url":"https://www.academia.edu/Documents/in/deoxycytidine"}],"urls":[{"id":36980424,"url":"https://doi.org/10.1007/s11095-016-1902-8"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277045"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277045/Enhanced_pH_Responsiveness_Cellular_Trafficking_Cytotoxicity_and_Long_circulation_of_PEGylated_Liposomes_with_Post_insertion_Technique_Using_Gemcitabine_as_a_Model_Drug"><img alt="Research paper thumbnail of Enhanced pH-Responsiveness, Cellular Trafficking, Cytotoxicity and Long-circulation of PEGylated Liposomes with Post-insertion Technique Using Gemcitabine as a Model Drug" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277045/Enhanced_pH_Responsiveness_Cellular_Trafficking_Cytotoxicity_and_Long_circulation_of_PEGylated_Liposomes_with_Post_insertion_Technique_Using_Gemcitabine_as_a_Model_Drug">Enhanced pH-Responsiveness, Cellular Trafficking, Cytotoxicity and Long-circulation of PEGylated Liposomes with Post-insertion Technique Using Gemcitabine as a Model Drug</a></div><div class="wp-workCard_item"><span>Pharmaceutical Research</span><span>, Feb 6, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The in vitro and in vivo properties of PEGylated pH-sensitive liposomes (PSL) prepared by pre- an...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The in vitro and in vivo properties of PEGylated pH-sensitive liposomes (PSL) prepared by pre- and post-insertion techniques were investigated. A pre-insertion or post-insertion technique was used for PSL PEGylation. For the first time, confocal laser scanning microscopy coupled with a modified calcein self-quench assay was applied to evaluate the endosome escape capability. PSL cellular uptake was evaluated using macrophages and the cytotoxicity using a gemcitabine (model drug)-resistant MIA PaCa-2 cells. The pharmacokinetics of PSL encapsulated gemcitabine was investigated in rats. PEGylation reduced the pH-sensitivity in a concentration-dependent manner (0.5-5% mol). Both PEGylation methods reduced the uptake of PSL by macrophages by over 60%. Cytotoxicity was ranked in the order: post-inserted PSL ≥ pre-inserted PSL &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; non-PSL &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; gemcitabine solution, consistent with the confocal microscopic observation and pH-sensitivity. Both pre and post-inserted PSL resulted in significant reductions (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) in plasma clearance (58.6 and 38.4 ml/h/kg), increases in the area-under-the-concentration-time curve (56.9 and 87.1 μM· h) and half-life (6.1 and 6.2 h) compared to gemcitabine solution (152.9 ml/h/kg, 22.2 μM· h and 1.4 h). PEGylation by post-insertion offers advantages over pre-insertion to obtain PSL with enhanced pH-sensitivity, more effective intra-cytoplasmic delivery, and a superior pharmacokinetics.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277045"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277045"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277045; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277045]").text(description); $(".js-view-count[data-work-id=111277045]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277045; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277045']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277045, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277045]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277045,"title":"Enhanced pH-Responsiveness, Cellular Trafficking, Cytotoxicity and Long-circulation of PEGylated Liposomes with Post-insertion Technique Using Gemcitabine as a Model Drug","translated_title":"","metadata":{"abstract":"The in vitro and in vivo properties of PEGylated pH-sensitive liposomes (PSL) prepared by pre- and post-insertion techniques were investigated. A pre-insertion or post-insertion technique was used for PSL PEGylation. For the first time, confocal laser scanning microscopy coupled with a modified calcein self-quench assay was applied to evaluate the endosome escape capability. PSL cellular uptake was evaluated using macrophages and the cytotoxicity using a gemcitabine (model drug)-resistant MIA PaCa-2 cells. The pharmacokinetics of PSL encapsulated gemcitabine was investigated in rats. PEGylation reduced the pH-sensitivity in a concentration-dependent manner (0.5-5% mol). Both PEGylation methods reduced the uptake of PSL by macrophages by over 60%. Cytotoxicity was ranked in the order: post-inserted PSL ≥ pre-inserted PSL \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; non-PSL \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; gemcitabine solution, consistent with the confocal microscopic observation and pH-sensitivity. Both pre and post-inserted PSL resulted in significant reductions (p \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) in plasma clearance (58.6 and 38.4 ml/h/kg), increases in the area-under-the-concentration-time curve (56.9 and 87.1 μM· h) and half-life (6.1 and 6.2 h) compared to gemcitabine solution (152.9 ml/h/kg, 22.2 μM· h and 1.4 h). PEGylation by post-insertion offers advantages over pre-insertion to obtain PSL with enhanced pH-sensitivity, more effective intra-cytoplasmic delivery, and a superior pharmacokinetics.","publisher":"Springer Science+Business Media","publication_date":{"day":6,"month":2,"year":2015,"errors":{}},"publication_name":"Pharmaceutical Research"},"translated_abstract":"The in vitro and in vivo properties of PEGylated pH-sensitive liposomes (PSL) prepared by pre- and post-insertion techniques were investigated. A pre-insertion or post-insertion technique was used for PSL PEGylation. For the first time, confocal laser scanning microscopy coupled with a modified calcein self-quench assay was applied to evaluate the endosome escape capability. PSL cellular uptake was evaluated using macrophages and the cytotoxicity using a gemcitabine (model drug)-resistant MIA PaCa-2 cells. The pharmacokinetics of PSL encapsulated gemcitabine was investigated in rats. PEGylation reduced the pH-sensitivity in a concentration-dependent manner (0.5-5% mol). Both PEGylation methods reduced the uptake of PSL by macrophages by over 60%. Cytotoxicity was ranked in the order: post-inserted PSL ≥ pre-inserted PSL \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; non-PSL \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; gemcitabine solution, consistent with the confocal microscopic observation and pH-sensitivity. Both pre and post-inserted PSL resulted in significant reductions (p \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) in plasma clearance (58.6 and 38.4 ml/h/kg), increases in the area-under-the-concentration-time curve (56.9 and 87.1 μM· h) and half-life (6.1 and 6.2 h) compared to gemcitabine solution (152.9 ml/h/kg, 22.2 μM· h and 1.4 h). PEGylation by post-insertion offers advantages over pre-insertion to obtain PSL with enhanced pH-sensitivity, more effective intra-cytoplasmic delivery, and a superior pharmacokinetics.","internal_url":"https://www.academia.edu/111277045/Enhanced_pH_Responsiveness_Cellular_Trafficking_Cytotoxicity_and_Long_circulation_of_PEGylated_Liposomes_with_Post_insertion_Technique_Using_Gemcitabine_as_a_Model_Drug","translated_internal_url":"","created_at":"2023-12-12T16:46:09.842-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Enhanced_pH_Responsiveness_Cellular_Trafficking_Cytotoxicity_and_Long_circulation_of_PEGylated_Liposomes_with_Post_insertion_Technique_Using_Gemcitabine_as_a_Model_Drug","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":11257,"name":"Drug delivery","url":"https://www.academia.edu/Documents/in/Drug_delivery"},{"id":17491,"name":"Macrophages","url":"https://www.academia.edu/Documents/in/Macrophages"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":90156,"name":"Endocytosis","url":"https://www.academia.edu/Documents/in/Endocytosis"},{"id":95655,"name":"Pharmaceutical","url":"https://www.academia.edu/Documents/in/Pharmaceutical"},{"id":129181,"name":"PEGylation","url":"https://www.academia.edu/Documents/in/PEGylation"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":302037,"name":"In Vivo","url":"https://www.academia.edu/Documents/in/In_Vivo"},{"id":390245,"name":"Particle Size","url":"https://www.academia.edu/Documents/in/Particle_Size"},{"id":1031068,"name":"Drug Carriers","url":"https://www.academia.edu/Documents/in/Drug_Carriers"},{"id":1135812,"name":"Drug Compounding","url":"https://www.academia.edu/Documents/in/Drug_Compounding"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1254280,"name":"Endosomes","url":"https://www.academia.edu/Documents/in/Endosomes"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"}],"urls":[{"id":36980423,"url":"https://doi.org/10.1007/s11095-015-1635-0"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277044"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277044/Development_of_High_Content_Gemcitabine_PEGylated_Liposomes_and_Their_Cytotoxicity_on_Drug_Resistant_Pancreatic_Tumour_Cells"><img alt="Research paper thumbnail of Development of High-Content Gemcitabine PEGylated Liposomes and Their Cytotoxicity on Drug-Resistant Pancreatic Tumour Cells" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277044/Development_of_High_Content_Gemcitabine_PEGylated_Liposomes_and_Their_Cytotoxicity_on_Drug_Resistant_Pancreatic_Tumour_Cells">Development of High-Content Gemcitabine PEGylated Liposomes and Their Cytotoxicity on Drug-Resistant Pancreatic Tumour Cells</a></div><div class="wp-workCard_item"><span>Pharmaceutical Research</span><span>, Mar 18, 2014</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The objective of this study was to develop high-content gemcitabine PEGylated liposomes to revers...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The objective of this study was to develop high-content gemcitabine PEGylated liposomes to reverse gemcitabine resistance in pancreatic tumour cells. The mechanism of drug loading into liposomes was also investigated. To increase the drug entrapment efficiency (EE) and drug loading (DL), a novel passive loading approach named Small Volume Incubation method (SVI) was developed and compared to the reverse phase evaporation (REV) and remote loading methods. The in vitro cytotoxicity was evaluated using MIA PaCa-2 and Panc-1 cell lines. The EE for remote loading was 12.3 ± 0.3%, much lower than expected and a burst release was observed with the resultant liposomes. Using the optimized SVI method, increased EE (37 ± 1%) and DL (4%, w/w) were obtained. The liposomes (200 ± 5 nm) showed minimal drug leakage, good stability, and significant improvement in cytotoxicity to the gemcitabine-resistant pancreatic cancer cell lines. Remote loading was not suitable for loading gemcitabine into liposomes. pKa &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4.6 for basic drugs and intra-liposomal precipitation of loaded compounds were suggested as an additional requirement to the current criteria for remote loading using ammonium sulphate gradient (pKa &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 11). High DL is essential for liposomes to reverse gemcitabine resistance in pancreatic cell lines.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277044"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277044"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277044; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277044]").text(description); $(".js-view-count[data-work-id=111277044]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277044; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277044']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277044, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277044]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277044,"title":"Development of High-Content Gemcitabine PEGylated Liposomes and Their Cytotoxicity on Drug-Resistant Pancreatic Tumour Cells","translated_title":"","metadata":{"abstract":"The objective of this study was to develop high-content gemcitabine PEGylated liposomes to reverse gemcitabine resistance in pancreatic tumour cells. The mechanism of drug loading into liposomes was also investigated. To increase the drug entrapment efficiency (EE) and drug loading (DL), a novel passive loading approach named Small Volume Incubation method (SVI) was developed and compared to the reverse phase evaporation (REV) and remote loading methods. The in vitro cytotoxicity was evaluated using MIA PaCa-2 and Panc-1 cell lines. The EE for remote loading was 12.3 ± 0.3%, much lower than expected and a burst release was observed with the resultant liposomes. Using the optimized SVI method, increased EE (37 ± 1%) and DL (4%, w/w) were obtained. The liposomes (200 ± 5 nm) showed minimal drug leakage, good stability, and significant improvement in cytotoxicity to the gemcitabine-resistant pancreatic cancer cell lines. Remote loading was not suitable for loading gemcitabine into liposomes. pKa \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4.6 for basic drugs and intra-liposomal precipitation of loaded compounds were suggested as an additional requirement to the current criteria for remote loading using ammonium sulphate gradient (pKa \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 11). High DL is essential for liposomes to reverse gemcitabine resistance in pancreatic cell lines.","publisher":"Springer Science+Business Media","publication_date":{"day":18,"month":3,"year":2014,"errors":{}},"publication_name":"Pharmaceutical Research"},"translated_abstract":"The objective of this study was to develop high-content gemcitabine PEGylated liposomes to reverse gemcitabine resistance in pancreatic tumour cells. The mechanism of drug loading into liposomes was also investigated. To increase the drug entrapment efficiency (EE) and drug loading (DL), a novel passive loading approach named Small Volume Incubation method (SVI) was developed and compared to the reverse phase evaporation (REV) and remote loading methods. The in vitro cytotoxicity was evaluated using MIA PaCa-2 and Panc-1 cell lines. The EE for remote loading was 12.3 ± 0.3%, much lower than expected and a burst release was observed with the resultant liposomes. Using the optimized SVI method, increased EE (37 ± 1%) and DL (4%, w/w) were obtained. The liposomes (200 ± 5 nm) showed minimal drug leakage, good stability, and significant improvement in cytotoxicity to the gemcitabine-resistant pancreatic cancer cell lines. Remote loading was not suitable for loading gemcitabine into liposomes. pKa \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4.6 for basic drugs and intra-liposomal precipitation of loaded compounds were suggested as an additional requirement to the current criteria for remote loading using ammonium sulphate gradient (pKa \u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 11). High DL is essential for liposomes to reverse gemcitabine resistance in pancreatic cell lines.","internal_url":"https://www.academia.edu/111277044/Development_of_High_Content_Gemcitabine_PEGylated_Liposomes_and_Their_Cytotoxicity_on_Drug_Resistant_Pancreatic_Tumour_Cells","translated_internal_url":"","created_at":"2023-12-12T16:46:09.585-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Development_of_High_Content_Gemcitabine_PEGylated_Liposomes_and_Their_Cytotoxicity_on_Drug_Resistant_Pancreatic_Tumour_Cells","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":9186,"name":"Pharmaceutical Technology","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Technology"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":26623,"name":"Pancreatic Cancer","url":"https://www.academia.edu/Documents/in/Pancreatic_Cancer"},{"id":95655,"name":"Pharmaceutical","url":"https://www.academia.edu/Documents/in/Pharmaceutical"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":390245,"name":"Particle Size","url":"https://www.academia.edu/Documents/in/Particle_Size"},{"id":405347,"name":"Pharmaceutical Formulation Technology","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Formulation_Technology"},{"id":440924,"name":"Surface Properties","url":"https://www.academia.edu/Documents/in/Surface_Properties"},{"id":1031068,"name":"Drug Carriers","url":"https://www.academia.edu/Documents/in/Drug_Carriers"},{"id":1135812,"name":"Drug Compounding","url":"https://www.academia.edu/Documents/in/Drug_Compounding"},{"id":1135814,"name":"Drug Stability","url":"https://www.academia.edu/Documents/in/Drug_Stability"},{"id":1157148,"name":"Cell Survival","url":"https://www.academia.edu/Documents/in/Cell_Survival"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"},{"id":1434630,"name":"Polyethylene Glycols","url":"https://www.academia.edu/Documents/in/Polyethylene_Glycols"},{"id":3521397,"name":"Pancreatic neoplasms","url":"https://www.academia.edu/Documents/in/Pancreatic_neoplasms"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":4132900,"name":"deoxycytidine ","url":"https://www.academia.edu/Documents/in/deoxycytidine"}],"urls":[{"id":36980422,"url":"https://doi.org/10.1007/s11095-014-1353-z"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277043"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277043/Brain_targeted_intranasal_delivery_of_dopamine_with_borneol_and_lactoferrin_co_modified_nanoparticles_for_treating_Parkinson_s_disease"><img alt="Research paper thumbnail of Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease" class="work-thumbnail" src="https://attachments.academia-assets.com/108858257/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277043/Brain_targeted_intranasal_delivery_of_dopamine_with_borneol_and_lactoferrin_co_modified_nanoparticles_for_treating_Parkinson_s_disease">Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease</a></div><div class="wp-workCard_item"><span>Drug Delivery</span><span>, 2019</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1834a5802a825d5cc6ac193c8b583185" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858257,&quot;asset_id&quot;:111277043,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858257/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277043"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277043"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277043; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277043]").text(description); $(".js-view-count[data-work-id=111277043]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277043; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277043']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277043, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "1834a5802a825d5cc6ac193c8b583185" } } $('.js-work-strip[data-work-id=111277043]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277043,"title":"Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease","translated_title":"","metadata":{"publisher":"Informa UK Limited","grobid_abstract":"Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC 0-12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p \u003c .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson's disease.","publication_date":{"day":null,"month":null,"year":2019,"errors":{}},"publication_name":"Drug Delivery","grobid_abstract_attachment_id":108858257},"translated_abstract":null,"internal_url":"https://www.academia.edu/111277043/Brain_targeted_intranasal_delivery_of_dopamine_with_borneol_and_lactoferrin_co_modified_nanoparticles_for_treating_Parkinson_s_disease","translated_internal_url":"","created_at":"2023-12-12T16:46:09.178-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858257,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858257/thumbnails/1.jpg","file_name":"10717544.2019.pdf","download_url":"https://www.academia.edu/attachments/108858257/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Brain_targeted_intranasal_delivery_of_do.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858257/10717544.2019-libre.pdf?1702428630=\u0026response-content-disposition=attachment%3B+filename%3DBrain_targeted_intranasal_delivery_of_do.pdf\u0026Expires=1732823519\u0026Signature=UxCWQ4idnM47VttJznWILMf-JH51f3tQAWEavrRwyUg2aNkxUqBXDEPrY6nZ45LvatpDHPYTB1icbdN0TE9WGbqu6s9UQwagfe8m9l-ePRDTA8RC9ShMrQWh~ogdbaNGRUb~ZlhXCHgDUu0gqx8PebX~Rfqb1115h3GYLp2kVxd2BDNjDwknfp9RsWNqA17rC9q0nbH0SvMSWNhG1LDV2hx2grRV2Y~L5o3lVZdbd9y-SqKu8Ot5HzdT4Lmkb1MXfBnUWI6tPL~6DWlSrY0be7TkPX5yojMF3maROLpnl11m23mgZ8MmwbASeO7sgBoBBUc71a~fKSYDSgMAil1iqw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Brain_targeted_intranasal_delivery_of_dopamine_with_borneol_and_lactoferrin_co_modified_nanoparticles_for_treating_Parkinson_s_disease","translated_slug":"","page_count":9,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858257,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858257/thumbnails/1.jpg","file_name":"10717544.2019.pdf","download_url":"https://www.academia.edu/attachments/108858257/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkxOSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Brain_targeted_intranasal_delivery_of_do.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858257/10717544.2019-libre.pdf?1702428630=\u0026response-content-disposition=attachment%3B+filename%3DBrain_targeted_intranasal_delivery_of_do.pdf\u0026Expires=1732823519\u0026Signature=UxCWQ4idnM47VttJznWILMf-JH51f3tQAWEavrRwyUg2aNkxUqBXDEPrY6nZ45LvatpDHPYTB1icbdN0TE9WGbqu6s9UQwagfe8m9l-ePRDTA8RC9ShMrQWh~ogdbaNGRUb~ZlhXCHgDUu0gqx8PebX~Rfqb1115h3GYLp2kVxd2BDNjDwknfp9RsWNqA17rC9q0nbH0SvMSWNhG1LDV2hx2grRV2Y~L5o3lVZdbd9y-SqKu8Ot5HzdT4Lmkb1MXfBnUWI6tPL~6DWlSrY0be7TkPX5yojMF3maROLpnl11m23mgZ8MmwbASeO7sgBoBBUc71a~fKSYDSgMAil1iqw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":11257,"name":"Drug delivery","url":"https://www.academia.edu/Documents/in/Drug_delivery"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":51566,"name":"Dopamine","url":"https://www.academia.edu/Documents/in/Dopamine"},{"id":302037,"name":"In Vivo","url":"https://www.academia.edu/Documents/in/In_Vivo"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980421,"url":"https://tandfonline.com/doi/pdf/10.1080/10717544.2019.1636420"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277042"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277042/Liposome_supported_peritoneal_dialysis_in_rat_amitriptyline_exposure_with_and_without_intravenous_lipid_emulsion"><img alt="Research paper thumbnail of Liposome supported peritoneal dialysis in rat amitriptyline exposure with and without intravenous lipid emulsion" class="work-thumbnail" src="https://attachments.academia-assets.com/108858256/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277042/Liposome_supported_peritoneal_dialysis_in_rat_amitriptyline_exposure_with_and_without_intravenous_lipid_emulsion">Liposome supported peritoneal dialysis in rat amitriptyline exposure with and without intravenous lipid emulsion</a></div><div class="wp-workCard_item"><span>Journal of liposome research</span><span>, Jan 5, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Liposome supported peritoneal dialysis is a recently described technique which may eventually be ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Liposome supported peritoneal dialysis is a recently described technique which may eventually be applicable in the clinical scenario of the intoxicated patient. We evaluated the hypothesis that intravenous injection of lipid emulsion (ILE) would augment acidic pH gradient liposome supported peritoneal dialysis (LSPD). Orogastrically amitriptyline dosed rats were treated with either Sodium bicarbonate (NaHCO3) intravenously and standard intraperitoneal dialysate (Group A); NaHCO3 intravenously and LSPD (Group B); or ILE and LSPD (Group C). The primary endpoint was dialysate amitriptyline concentration after a 60 min dwell. Secondary analysis included an estimate of extraction ratio for peritoneal blood flow (ERs). There were significantly higher intraperitoneal concentrations of amitriptyline and ERs in the two groups treated with LSPD (Group B, p = 0.02, Group C, p &amp;lt; 0.01 vs. Group A). There was no observed effect for ILE on intraperitoneal amitriptyline concentration or ERs (p &amp;...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="8148ad461ceb427f0d0e98b37a4d191e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858256,&quot;asset_id&quot;:111277042,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858256/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277042"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277042"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277042; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277042]").text(description); $(".js-view-count[data-work-id=111277042]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277042; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277042']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277042, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "8148ad461ceb427f0d0e98b37a4d191e" } } $('.js-work-strip[data-work-id=111277042]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277042,"title":"Liposome supported peritoneal dialysis in rat amitriptyline exposure with and without intravenous lipid emulsion","translated_title":"","metadata":{"abstract":"Liposome supported peritoneal dialysis is a recently described technique which may eventually be applicable in the clinical scenario of the intoxicated patient. We evaluated the hypothesis that intravenous injection of lipid emulsion (ILE) would augment acidic pH gradient liposome supported peritoneal dialysis (LSPD). Orogastrically amitriptyline dosed rats were treated with either Sodium bicarbonate (NaHCO3) intravenously and standard intraperitoneal dialysate (Group A); NaHCO3 intravenously and LSPD (Group B); or ILE and LSPD (Group C). The primary endpoint was dialysate amitriptyline concentration after a 60 min dwell. Secondary analysis included an estimate of extraction ratio for peritoneal blood flow (ERs). There were significantly higher intraperitoneal concentrations of amitriptyline and ERs in the two groups treated with LSPD (Group B, p = 0.02, Group C, p \u0026lt; 0.01 vs. Group A). There was no observed effect for ILE on intraperitoneal amitriptyline concentration or ERs (p \u0026...","publication_date":{"day":5,"month":1,"year":2017,"errors":{}},"publication_name":"Journal of liposome research"},"translated_abstract":"Liposome supported peritoneal dialysis is a recently described technique which may eventually be applicable in the clinical scenario of the intoxicated patient. We evaluated the hypothesis that intravenous injection of lipid emulsion (ILE) would augment acidic pH gradient liposome supported peritoneal dialysis (LSPD). Orogastrically amitriptyline dosed rats were treated with either Sodium bicarbonate (NaHCO3) intravenously and standard intraperitoneal dialysate (Group A); NaHCO3 intravenously and LSPD (Group B); or ILE and LSPD (Group C). The primary endpoint was dialysate amitriptyline concentration after a 60 min dwell. Secondary analysis included an estimate of extraction ratio for peritoneal blood flow (ERs). There were significantly higher intraperitoneal concentrations of amitriptyline and ERs in the two groups treated with LSPD (Group B, p = 0.02, Group C, p \u0026lt; 0.01 vs. Group A). There was no observed effect for ILE on intraperitoneal amitriptyline concentration or ERs (p \u0026...","internal_url":"https://www.academia.edu/111277042/Liposome_supported_peritoneal_dialysis_in_rat_amitriptyline_exposure_with_and_without_intravenous_lipid_emulsion","translated_internal_url":"","created_at":"2023-12-12T16:46:08.991-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858256,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858256/thumbnails/1.jpg","file_name":"15191549.pdf","download_url":"https://www.academia.edu/attachments/108858256/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Liposome_supported_peritoneal_dialysis_i.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858256/15191549-libre.pdf?1702428624=\u0026response-content-disposition=attachment%3B+filename%3DLiposome_supported_peritoneal_dialysis_i.pdf\u0026Expires=1732823520\u0026Signature=S1K~y-On4eZ-cwtlUQM9Dax5TLXmSAny8DUtV3rQ9FnjCF6fyiIEgc3qB~tBml5q2NjCiZ2O2IDNVj09577X6tfI3KKm1sEyawNjbmPaubmMw~n5k-knj576qEGkW6HoENMkfS17FhUCHu9ksSQ-B3ACIZVPv~WFP4yi-Z~qP7AK9ItlC7UYeLWxU6Zsw-8EFGBnE7rGdAr14Hw80xvnbcmIqkrscGBOmxAI4RQdPuFaD-VpGlnNVsuPonVPSQwJBvyVHXJIkyctVxvcT5jF8PmtYrkuOBbKP7ovQwtqvm6bKN196EsCy-zPwAqvLoY4gmEPI5aOZq5VXBqM8w9c0g__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Liposome_supported_peritoneal_dialysis_in_rat_amitriptyline_exposure_with_and_without_intravenous_lipid_emulsion","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858256,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858256/thumbnails/1.jpg","file_name":"15191549.pdf","download_url":"https://www.academia.edu/attachments/108858256/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Liposome_supported_peritoneal_dialysis_i.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858256/15191549-libre.pdf?1702428624=\u0026response-content-disposition=attachment%3B+filename%3DLiposome_supported_peritoneal_dialysis_i.pdf\u0026Expires=1732823520\u0026Signature=S1K~y-On4eZ-cwtlUQM9Dax5TLXmSAny8DUtV3rQ9FnjCF6fyiIEgc3qB~tBml5q2NjCiZ2O2IDNVj09577X6tfI3KKm1sEyawNjbmPaubmMw~n5k-knj576qEGkW6HoENMkfS17FhUCHu9ksSQ-B3ACIZVPv~WFP4yi-Z~qP7AK9ItlC7UYeLWxU6Zsw-8EFGBnE7rGdAr14Hw80xvnbcmIqkrscGBOmxAI4RQdPuFaD-VpGlnNVsuPonVPSQwJBvyVHXJIkyctVxvcT5jF8PmtYrkuOBbKP7ovQwtqvm6bKN196EsCy-zPwAqvLoY4gmEPI5aOZq5VXBqM8w9c0g__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":145,"name":"Biochemistry","url":"https://www.academia.edu/Documents/in/Biochemistry"},{"id":158,"name":"Marine Biology","url":"https://www.academia.edu/Documents/in/Marine_Biology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":1524,"name":"Science Policy","url":"https://www.academia.edu/Documents/in/Science_Policy"},{"id":2513,"name":"Molecular Biology","url":"https://www.academia.edu/Documents/in/Molecular_Biology"},{"id":4553,"name":"Toxicology","url":"https://www.academia.edu/Documents/in/Toxicology"},{"id":5398,"name":"Biotechnology","url":"https://www.academia.edu/Documents/in/Biotechnology"},{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer"},{"id":13827,"name":"Cell Biology","url":"https://www.academia.edu/Documents/in/Cell_Biology"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":447741,"name":"Peritoneal Dialysis","url":"https://www.academia.edu/Documents/in/Peritoneal_Dialysis"},{"id":1508487,"name":"Amitriptyline","url":"https://www.academia.edu/Documents/in/Amitriptyline"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277041"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277041/Effects_of_GHK_Cu_on_MMP_and_TIMP_Expression_Collagen_and_Elastin_Production_and_Facial_Wrinkle_Parameters"><img alt="Research paper thumbnail of Effects of GHK-Cu on MMP and TIMP Expression, Collagen and Elastin Production, and Facial Wrinkle Parameters" class="work-thumbnail" src="https://attachments.academia-assets.com/108858255/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277041/Effects_of_GHK_Cu_on_MMP_and_TIMP_Expression_Collagen_and_Elastin_Production_and_Facial_Wrinkle_Parameters">Effects of GHK-Cu on MMP and TIMP Expression, Collagen and Elastin Production, and Facial Wrinkle Parameters</a></div><div class="wp-workCard_item"><span>Journal of Aging Science</span><span>, 2016</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5f2a15fd11f9b407665659fedac45e31" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858255,&quot;asset_id&quot;:111277041,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858255/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277041"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277041"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277041; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277041]").text(description); $(".js-view-count[data-work-id=111277041]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277041; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277041']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277041, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5f2a15fd11f9b407665659fedac45e31" } } $('.js-work-strip[data-work-id=111277041]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277041,"title":"Effects of GHK-Cu on MMP and TIMP Expression, Collagen and Elastin Production, and Facial Wrinkle Parameters","translated_title":"","metadata":{"publisher":"OMICS Publishing Group","grobid_abstract":"Background: Glycyl-L-histidyl-L-lysine-copper (GHK-Cu) is an endogenous tripeptide-copper complex involved in collagen synthesis and is used topically as a skin anti-aging and wound healing agent. However, its biological effects are yet to be fully elucidated. Objectives: To investigate the effects of GHK-Cu on gene expression of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), and on production of collagen and elastin by human adult dermal fibroblasts (HDFa); and to investigate the effectiveness of topical application of GHK-Cu on wrinkle parameters in volunteers. Methods: Cultured HDFa were incubated with GHK-Cu at 0.01, 1 and 100 nM in cell culture medium. Gene expression (mRNA) for MMP1, MMP2, TIMP1 and TIMP2 in treated and control HDFa was measured by RT-PCR. Cellular production of collagen and elastin was measured colourmetrically using commercial assay kits. Correlations between gene expression and collagen and elastin production were determined. A randomised, double-blind clinical trial involving twice daily application of GHK-Cu, encapsulated in lipid-based nano-carrier, to facial skin of female subjects (n= 40, aged 40 to 65) was run over 8 weeks. The formulation vehicle (a serum) and a commercial cosmetic product containing Matrixyl ® 3000, a lipophilic GHK derivative, were used as controls. Results: GHK-Cu significantly increased gene expression of MMP1 and MMP2 at the lowest concentration whilst simultaneously increasing the expression of TIMP1 at all the tested concentrations. All examined concentrations of GHK-Cu increased both collagen and elastin production. An increase of the mRNA expression ratio of TIMPs to MMPs was associated with an increase in collagen/elastin production. Application of GHK-Cu in nano-carriers to facial skin of volunteers significantly reduced wrinkle volume (31.6%; p=0.004) compared to Matrixyl ® 3000, and significantly reduced wrinkle volume (55.8%; p\u003c0.001) and wrinkle depth (32.8%; p=0.012) compared to control serum. Conclusions: GHK-Cu significantly increased collagen and elastin production by HDFa cells depending on the relative mRNA expression of their TIMP(s) over MMP. Topical application of GHK-Cu with the aid of nano-carriers reduced wrinkle volume to a significantly greater extent than the vehicle alone or a commercial product containing Matrixyl 3000 ® , a GHK lipophilic derivative.","publication_date":{"day":null,"month":null,"year":2016,"errors":{}},"publication_name":"Journal of Aging Science","grobid_abstract_attachment_id":108858255},"translated_abstract":null,"internal_url":"https://www.academia.edu/111277041/Effects_of_GHK_Cu_on_MMP_and_TIMP_Expression_Collagen_and_Elastin_Production_and_Facial_Wrinkle_Parameters","translated_internal_url":"","created_at":"2023-12-12T16:46:08.842-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858255,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858255/thumbnails/1.jpg","file_name":"4298d633ec602468b9b43d1730baede1de5d.pdf","download_url":"https://www.academia.edu/attachments/108858255/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effects_of_GHK_Cu_on_MMP_and_TIMP_Expres.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858255/4298d633ec602468b9b43d1730baede1de5d-libre.pdf?1702428639=\u0026response-content-disposition=attachment%3B+filename%3DEffects_of_GHK_Cu_on_MMP_and_TIMP_Expres.pdf\u0026Expires=1732823520\u0026Signature=X5pj-7M6~9WO4eh4tzD7~XiC21vL-QmnJGZJgnRVxitmeECymbcT1VFXuVj-jiaqYYHs41f~LgVm-MZ1E2ebY2DTRjzsXFpvQ80CD9C63krq6guKf0fx7zQNCN7mQOgOZ8ELm0Ymfz9ZU-DC~pkWbo2qVpjG~tEzo-vYBFpVWJWXTHNbDpAxp05mP1~Eiaco~-eIz-0a9Xy82eITbPRMmdXrR8rKVeper1wNLK1P0e8hOlUMZyFv3i8QmGuN4krmikb96f0~Q1QxkEyExgxSdKBqvlbTWTvaypetOsWjvGeyDj2pyf0GvQTLP7lepnPoXLA0nVOwYkfakbQ7VcRT-A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Effects_of_GHK_Cu_on_MMP_and_TIMP_Expression_Collagen_and_Elastin_Production_and_Facial_Wrinkle_Parameters","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858255,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858255/thumbnails/1.jpg","file_name":"4298d633ec602468b9b43d1730baede1de5d.pdf","download_url":"https://www.academia.edu/attachments/108858255/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Effects_of_GHK_Cu_on_MMP_and_TIMP_Expres.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858255/4298d633ec602468b9b43d1730baede1de5d-libre.pdf?1702428639=\u0026response-content-disposition=attachment%3B+filename%3DEffects_of_GHK_Cu_on_MMP_and_TIMP_Expres.pdf\u0026Expires=1732823520\u0026Signature=X5pj-7M6~9WO4eh4tzD7~XiC21vL-QmnJGZJgnRVxitmeECymbcT1VFXuVj-jiaqYYHs41f~LgVm-MZ1E2ebY2DTRjzsXFpvQ80CD9C63krq6guKf0fx7zQNCN7mQOgOZ8ELm0Ymfz9ZU-DC~pkWbo2qVpjG~tEzo-vYBFpVWJWXTHNbDpAxp05mP1~Eiaco~-eIz-0a9Xy82eITbPRMmdXrR8rKVeper1wNLK1P0e8hOlUMZyFv3i8QmGuN4krmikb96f0~Q1QxkEyExgxSdKBqvlbTWTvaypetOsWjvGeyDj2pyf0GvQTLP7lepnPoXLA0nVOwYkfakbQ7VcRT-A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":350926,"name":"Elastin","url":"https://www.academia.edu/Documents/in/Elastin"},{"id":1920779,"name":"Matrix Metalloproteinase","url":"https://www.academia.edu/Documents/in/Matrix_Metalloproteinase"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277040"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277040/Reversal_of_lipophilic_weak_bases_using_pH_gradient_acidic_centre_liposomes_demonstration_of_effect_in_dabigatran_induced_anticoagulation"><img alt="Research paper thumbnail of Reversal of lipophilic weak bases using pH gradient acidic centre liposomes: demonstration of effect in dabigatran-induced anticoagulation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277040/Reversal_of_lipophilic_weak_bases_using_pH_gradient_acidic_centre_liposomes_demonstration_of_effect_in_dabigatran_induced_anticoagulation">Reversal of lipophilic weak bases using pH gradient acidic centre liposomes: demonstration of effect in dabigatran-induced anticoagulation</a></div><div class="wp-workCard_item"><span>Clinical toxicology (Philadelphia, Pa.)</span><span>, Jan 29, 2016</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Liposomes have recently emerged as rational vehicles for drug detoxification. Modification of the...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Liposomes have recently emerged as rational vehicles for drug detoxification. Modification of the core pH may further enhance the ability of liposomes to sequester lipophilic toxins that are weak bases. Dabigatran, a reversible inhibitor of thrombin, has been widely promoted as a novel oral anticoagulant. As a lipophilic weak-base, it provides a rational target for reversal with acidic-centred liposomal preparations. The present study tests the hypothesis that acidic centre liposomes will reverse dabigatran induced anticoagulation. Following enteric dabigatran dosing in vitro assessment of thrombin clotting times (TCT) was undertaken in rabbit plasma spiked with incremental liposome concentrations. Tail vein bleeding was assessed following intravenous liposome injection in rats after enteric dabigatran administration. Liposomes achieved reversal of TCT to baseline at low levels of thrombin inhibition, and partial reversal of TCT at higher levels. Liposomes completely reversed the ef...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277040"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277040"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277040; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277040]").text(description); $(".js-view-count[data-work-id=111277040]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277040; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277040']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277040, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277040]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277040,"title":"Reversal of lipophilic weak bases using pH gradient acidic centre liposomes: demonstration of effect in dabigatran-induced anticoagulation","translated_title":"","metadata":{"abstract":"Liposomes have recently emerged as rational vehicles for drug detoxification. Modification of the core pH may further enhance the ability of liposomes to sequester lipophilic toxins that are weak bases. Dabigatran, a reversible inhibitor of thrombin, has been widely promoted as a novel oral anticoagulant. As a lipophilic weak-base, it provides a rational target for reversal with acidic-centred liposomal preparations. The present study tests the hypothesis that acidic centre liposomes will reverse dabigatran induced anticoagulation. Following enteric dabigatran dosing in vitro assessment of thrombin clotting times (TCT) was undertaken in rabbit plasma spiked with incremental liposome concentrations. Tail vein bleeding was assessed following intravenous liposome injection in rats after enteric dabigatran administration. Liposomes achieved reversal of TCT to baseline at low levels of thrombin inhibition, and partial reversal of TCT at higher levels. Liposomes completely reversed the ef...","publication_date":{"day":29,"month":1,"year":2016,"errors":{}},"publication_name":"Clinical toxicology (Philadelphia, Pa.)"},"translated_abstract":"Liposomes have recently emerged as rational vehicles for drug detoxification. Modification of the core pH may further enhance the ability of liposomes to sequester lipophilic toxins that are weak bases. Dabigatran, a reversible inhibitor of thrombin, has been widely promoted as a novel oral anticoagulant. As a lipophilic weak-base, it provides a rational target for reversal with acidic-centred liposomal preparations. The present study tests the hypothesis that acidic centre liposomes will reverse dabigatran induced anticoagulation. Following enteric dabigatran dosing in vitro assessment of thrombin clotting times (TCT) was undertaken in rabbit plasma spiked with incremental liposome concentrations. Tail vein bleeding was assessed following intravenous liposome injection in rats after enteric dabigatran administration. Liposomes achieved reversal of TCT to baseline at low levels of thrombin inhibition, and partial reversal of TCT at higher levels. Liposomes completely reversed the ef...","internal_url":"https://www.academia.edu/111277040/Reversal_of_lipophilic_weak_bases_using_pH_gradient_acidic_centre_liposomes_demonstration_of_effect_in_dabigatran_induced_anticoagulation","translated_internal_url":"","created_at":"2023-12-12T16:46:08.446-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Reversal_of_lipophilic_weak_bases_using_pH_gradient_acidic_centre_liposomes_demonstration_of_effect_in_dabigatran_induced_anticoagulation","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":61099,"name":"Thrombin","url":"https://www.academia.edu/Documents/in/Thrombin"},{"id":115194,"name":"Clinical Toxicology","url":"https://www.academia.edu/Documents/in/Clinical_Toxicology"},{"id":147066,"name":"Liposomes","url":"https://www.academia.edu/Documents/in/Liposomes"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":189424,"name":"Blood Coagulation","url":"https://www.academia.edu/Documents/in/Blood_Coagulation"},{"id":189949,"name":"Anticoagulants","url":"https://www.academia.edu/Documents/in/Anticoagulants"},{"id":302037,"name":"In Vivo","url":"https://www.academia.edu/Documents/in/In_Vivo"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":413195,"name":"Time Factors","url":"https://www.academia.edu/Documents/in/Time_Factors"},{"id":482750,"name":"Dabigatran","url":"https://www.academia.edu/Documents/in/Dabigatran"},{"id":788677,"name":"Rabbits","url":"https://www.academia.edu/Documents/in/Rabbits"},{"id":1004785,"name":"Hemorrhage","url":"https://www.academia.edu/Documents/in/Hemorrhage"},{"id":1137254,"name":"Hydrogen-Ion Concentration","url":"https://www.academia.edu/Documents/in/Hydrogen-Ion_Concentration"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277038"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277038/Niosomes_and_discomes_for_ocular_delivery_of_naltrexone_hydrochloride_Morphological_rheological_spreading_properties_and_photo_protective_effects"><img alt="Research paper thumbnail of Niosomes and discomes for ocular delivery of naltrexone hydrochloride: Morphological, rheological, spreading properties and photo-protective effects" class="work-thumbnail" src="https://attachments.academia-assets.com/108858284/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277038/Niosomes_and_discomes_for_ocular_delivery_of_naltrexone_hydrochloride_Morphological_rheological_spreading_properties_and_photo_protective_effects">Niosomes and discomes for ocular delivery of naltrexone hydrochloride: Morphological, rheological, spreading properties and photo-protective effects</a></div><div class="wp-workCard_item"><span>International Journal of Pharmaceutics</span><span>, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="5216a7c8a1a3aef5e9548ac3daea6c5d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858284,&quot;asset_id&quot;:111277038,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858284/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277038"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277038"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277038; 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "5216a7c8a1a3aef5e9548ac3daea6c5d" } } $('.js-work-strip[data-work-id=111277038]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277038,"title":"Niosomes and discomes for ocular delivery of naltrexone hydrochloride: Morphological, rheological, spreading properties and photo-protective effects","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"Naltrexone hydrochloride (NTX) is a promising treatment for corneal disorders linked to diabetes mellitus (diabetic keratopathy). However, NTX has a major stability problem due to autoxidation, which is likely to hinder its formulation as eye drops for treatment of diabetic keratopathy. In this study, in-house developed NTX non-ionic surfactant vesicles (niosomes and discomes) were evaluated for their spreading, rheological properties and their ability to impede the inevitable autoxidation of NTX in aqueous solutions. The measured contact angles and spreading coefficients for niosomes reflected significantly (P \u003c 0.05) better wetting and spreading abilities than the aqueous vehicle. The prepared niosomes were significantly more viscous (P \u003c 0.05) than the aqueous solution. The lipid content, size and composition of niosomes are the main factors affecting the viscosity of niosomal dispersions. Exposure of NTX solution to artificial daylight illumination (10,000 lux) can produce extensive degradation of NTX due to oxidation. The prepared formulations were able to significantly (P \u003c 0.05) protect the encapsulated NTX from the photo-induced oxidation compared with free NTX solutions. The investigated niosomes lend themselves as a potential ocular delivery modality for NTX.","publication_date":{"day":null,"month":null,"year":2012,"errors":{}},"publication_name":"International Journal of 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src="https://attachments.academia-assets.com/108858287/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277036/In_situ_phase_transition_from_microemulsion_to_liquid_crystal_with_the_potential_of_prolonged_parenteral_drug_delivery">In-situ phase transition from microemulsion to liquid crystal with the potential of prolonged parenteral drug delivery</a></div><div class="wp-workCard_item"><span>International Journal of Pharmaceutics</span><span>, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="e62ddef1db2d06654be3aa34622961d4" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858287,&quot;asset_id&quot;:111277036,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858287/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277036"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277036"><i class="fa fa-spinner fa-spin"></i></span><script>$(function 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});</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "e62ddef1db2d06654be3aa34622961d4" } } $('.js-work-strip[data-work-id=111277036]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277036,"title":"In-situ phase transition from microemulsion to liquid crystal with the potential of prolonged parenteral drug delivery","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"This study is the first to investigate and demonstrate the potential of microemulsions (MEs) for sustained release parenteral drug delivery, due to phase transition behavior in aqueous environments. Phase diagrams were constructed with Miglyol 812N oil and a blend of (co)surfactants Solutol HS 15 and Span 80 with ethanol. Liquid crystal (LC) and coarse emulsion (CE) regions were found adjacent to the ME region in the water-rich corner of the phase diagram. Two formulations were selected, a LC-forming ME and a CE-forming ME and each were investigated with respect to their rheology, particle size, drug release profiles and particularly, the phase transition behavior. The spreadability in an aqueous environment was determined and release profiles from MEs were generated with gamma-scintigraphy. The CE-forming ME dispersed readily in an aqueous environment, whereas the LC-forming ME remained in a contracted region possibly due to the transition of ME to LC at the water/ME interface. Gamma-scintigraphy showed that the LC-forming ME had minimal spreadability and a slow release of 99m Tc in the first-order manner, suggesting phase conversion at the interface. In conclusion, owing to the potential of phase transition, LCforming MEs could be used as extravascular injectable drug delivery vehicles for prolonged drug release.","publication_date":{"day":null,"month":null,"year":2012,"errors":{}},"publication_name":"International Journal of 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sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980416,"url":"https://api.elsevier.com/content/article/PII:S0378517312003663?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277033"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277033/Absorption_and_tissue_tolerance_of_ricobendazole_in_the_presence_of_hydroxypropyl_%CE%B2_cyclodextrin_following_subcutaneous_injection_in_sheep"><img alt="Research paper thumbnail of Absorption and tissue tolerance of ricobendazole in the presence of hydroxypropyl-β-cyclodextrin following subcutaneous injection in sheep" class="work-thumbnail" src="https://attachments.academia-assets.com/108858254/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277033/Absorption_and_tissue_tolerance_of_ricobendazole_in_the_presence_of_hydroxypropyl_%CE%B2_cyclodextrin_following_subcutaneous_injection_in_sheep">Absorption and tissue tolerance of ricobendazole in the presence of hydroxypropyl-β-cyclodextrin following subcutaneous injection in sheep</a></div><div class="wp-workCard_item"><span>International Journal of Pharmaceutics</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="41219d67105f437ffc70337b201ba4e5" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858254,&quot;asset_id&quot;:111277033,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858254/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277033"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277033"><i class="fa fa-spinner fa-spin"></i></span><script>$(function 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});</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "41219d67105f437ffc70337b201ba4e5" } } $('.js-work-strip[data-work-id=111277033]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277033,"title":"Absorption and tissue tolerance of ricobendazole in the presence of hydroxypropyl-β-cyclodextrin following subcutaneous injection in sheep","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"Post-injection precipitation may cause poor and erratic drug absorption and tissue irritation at the injection site. Tissue tolerance and pharmacokinetics of a low pH ricobendazole (RBZ) injectable containing 20% hydroxypropyl-␤-cyclodextrin (HP-␤-CD) were simultaneously investigated after subcutaneous injection in sheep compared to a reference formulation without HP-␤-CD. Each animal received a RBZ containing formulation on one side of the back and the respective vehicle on the contralateral side. The HP-␤-CD vehicle showed good tissue tolerance and the acidic solution caused minimal injection site reactions. Both RBZ containing formulations caused pain on injection and tissue histological changes in some animals. Lack of elevation of plasma creatine kinase indicated that none of the formulations caused significant damage to the underlying muscle tissue. Compared to the reference formulation, AUC and C max of the HP-␤-CD formulation were 1.6 and 2.2 times higher, respectively, whereas t max , MRT and t 1/2 were significantly shorter suggesting faster and greater absorption of RBZ in the presence of HP-␤-CD. This was attributed to the effect of inhibition of post-injection drug precipitation and drug absorption enhancement of HP-␤-CD. In conclusion, HP-␤-CD was shown to be a tissue-compatible excipient with potential to inhibit post-injection precipitation and increase absorption of poorly water soluble drugs. Additionally, the HP-␤-CD formulation showed promise as an injectable that potentially minimizes irritation by reducing the dose required.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"International Journal of 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$a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277031"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277031/Conjunctival_and_corneal_tolerability_assessment_of_ocular_naltrexone_niosomes_and_their_ingredients_on_the_hens_egg_chorioallantoic_membrane_and_excised_bovine_cornea_models"><img alt="Research paper thumbnail of Conjunctival and corneal tolerability assessment of ocular naltrexone niosomes and their ingredients on the hen&#39;s egg chorioallantoic membrane and excised bovine cornea models" class="work-thumbnail" src="https://attachments.academia-assets.com/108858253/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277031/Conjunctival_and_corneal_tolerability_assessment_of_ocular_naltrexone_niosomes_and_their_ingredients_on_the_hens_egg_chorioallantoic_membrane_and_excised_bovine_cornea_models">Conjunctival and corneal tolerability assessment of ocular naltrexone niosomes and their ingredients on the hen&#39;s egg chorioallantoic membrane and excised bovine cornea models</a></div><div class="wp-workCard_item"><span>International Journal of Pharmaceutics</span><span>, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="beeb697a2b6f1eba21df2b7f85b30523" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858253,&quot;asset_id&quot;:111277031,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" 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})(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "beeb697a2b6f1eba21df2b7f85b30523" } } $('.js-work-strip[data-work-id=111277031]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277031,"title":"Conjunctival and corneal tolerability assessment of ocular naltrexone niosomes and their ingredients on the hen's egg chorioallantoic membrane and excised bovine cornea models","translated_title":"","metadata":{"publisher":"Elsevier BV","grobid_abstract":"This study aimed at combining the hen's egg test-chorioallantoic membrane (HET-CAM), bovine corneal opacity and permeability (BCOP) test and histological examination of excised corneas to evaluate the conjunctival and corneal toxicity of niosomes and their ingredients. Various surfactant/lipid combinations and concentrations (1-10%, w/v) were investigated for the ocular delivery of an ambitious drug (naltrexone hydrochloride) for treatment of diabetic keratopathy. Four niosomal formulations were investigated and found to be non irritant to the 10 days old HET-CAMs (an acceptable conjunctival model). Only one of the tested ingredients (sodium cholate-CH) showed moderate irritation, however such an effect was diminished when incorporated into niosomes. Corneal opacity and fluorescein permeability scores for the test substances correlated well with the HET-CAM test results. Corneal erosion and stromal thickness were found to be in agreement with the HET-CAM and BCOP results, which discriminated well between moderately and mildly irritant test substances. Corneal histological examination revealed toxicity signs included epithelial erosion, stromal condensation and stromal vacuolisation, which allowed better discrimination between strong and moderate irritants. It is concluded that the prepared niosomes possess good ocular tolerability and minimal ocular tissue irritation. They can be further investigated as ocular delivery systems using appropriate animal models.","publication_date":{"day":null,"month":null,"year":2012,"errors":{}},"publication_name":"International Journal of 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Opacity","url":"https://www.academia.edu/Documents/in/Corneal_Opacity"},{"id":402759,"name":"Chickens","url":"https://www.academia.edu/Documents/in/Chickens"},{"id":767931,"name":"Naltrexone","url":"https://www.academia.edu/Documents/in/Naltrexone"},{"id":1384707,"name":"Niosomes","url":"https://www.academia.edu/Documents/in/Niosomes"},{"id":2534790,"name":"Chorioallantoic Membrane","url":"https://www.academia.edu/Documents/in/Chorioallantoic_Membrane"},{"id":2641150,"name":"Tolerability","url":"https://www.academia.edu/Documents/in/Tolerability"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"},{"id":3881526,"name":"In Vitro Techniques","url":"https://www.academia.edu/Documents/in/In_Vitro_Techniques"}],"urls":[{"id":36980412,"url":"https://api.elsevier.com/content/article/PII:S0378517312004097?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277029"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277029/In_vitro_prediction_of_bioavailability_following_extravascular_injection_of_poorly_soluble_drugs_an_insight_into_clinical_failure_and_the_role_of_delivery_systems"><img alt="Research paper thumbnail of In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems" class="work-thumbnail" src="https://attachments.academia-assets.com/108858216/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277029/In_vitro_prediction_of_bioavailability_following_extravascular_injection_of_poorly_soluble_drugs_an_insight_into_clinical_failure_and_the_role_of_delivery_systems">In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems</a></div><div class="wp-workCard_item"><span>Journal of Pharmacy and Pharmacology</span><span>, 2013</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Objectives To investigate the feasibility of using an in-vitro model to simulate the incidence of...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Objectives To investigate the feasibility of using an in-vitro model to simulate the incidence of post-injection drug precipitation (PDP), and to identify the roles of drug properties and delivery systems in its occurrence. Methods A literature review on incomplete absorption following extravascular injection (subcutaneous and intramuscular) was conducted. Six model drugs in nine different formulations were studied for an in-vitro/in-vivo correlation. A rapid in-vitro dilution method using a 96-well plate was used for predicting PDP by dilution with a physiological buffer. New formulations based on hydroxypropyl-β-cyclodextrin (CD), with and without co-solvents or pH control, were developed and tested on the in-vitro model. Key findings The occurrence of precipitation detected from the in-vitro dilution model appeared to be correlated with clinical reports and animal studies. The formulation components played an important role in determining the potential for drug precipitation on d...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ddb26841f330c37f5c2ef4c966a049b2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858216,&quot;asset_id&quot;:111277029,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858216/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277029"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277029"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277029; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277029]").text(description); $(".js-view-count[data-work-id=111277029]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277029; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277029']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277029, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ddb26841f330c37f5c2ef4c966a049b2" } } $('.js-work-strip[data-work-id=111277029]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277029,"title":"In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems","translated_title":"","metadata":{"abstract":"Objectives To investigate the feasibility of using an in-vitro model to simulate the incidence of post-injection drug precipitation (PDP), and to identify the roles of drug properties and delivery systems in its occurrence. Methods A literature review on incomplete absorption following extravascular injection (subcutaneous and intramuscular) was conducted. Six model drugs in nine different formulations were studied for an in-vitro/in-vivo correlation. A rapid in-vitro dilution method using a 96-well plate was used for predicting PDP by dilution with a physiological buffer. New formulations based on hydroxypropyl-β-cyclodextrin (CD), with and without co-solvents or pH control, were developed and tested on the in-vitro model. Key findings The occurrence of precipitation detected from the in-vitro dilution model appeared to be correlated with clinical reports and animal studies. 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The formulation components played an important role in determining the potential for drug precipitation on 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data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277026/Physicochemical_Characterization_of_Ricobendazole_I_Solubility_Lipophilicity_and_Ionization_Characteristics"><img alt="Research paper thumbnail of Physicochemical Characterization of Ricobendazole: I. Solubility, Lipophilicity, and Ionization Characteristics" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277026/Physicochemical_Characterization_of_Ricobendazole_I_Solubility_Lipophilicity_and_Ionization_Characteristics">Physicochemical Characterization of Ricobendazole: I. Solubility, Lipophilicity, and Ionization Characteristics</a></div><div class="wp-workCard_item"><span>Journal of Pharmaceutical Sciences</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The physicochemical properties of ricobendazole (RBZ) were characterized using conventional metho...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The physicochemical properties of ricobendazole (RBZ) were characterized using conventional methods. Solubility in some pharmaceutical solvents, pH-solubility, ionization properties, and lipophilicity are described. The solubility of RBZ in water is 62 mug/mL and very poor in common pharmaceutical solvents, for example, oils (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.25 mg/mL in all the tested oils) or ethanol (1.2 mg/mL) and propylene glycol (2.6 mg/mL), and slightly higher in dipolar solvents, DMSO (16.5 mg/mL). U-shaped pH-solubility profile in aqueous solutions indicates RBZ is an ampholyte. pK(a) values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 for the basic group and 9.82 and 9.53 for the non-basic nitrogen, respectively. Combination of low pH and surfactant/co-solvent mixtures also improved solubility. RBZ formed a 1:1 complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a binding constant (K(1:1)) of 311/M1. Apparent partition coefficients of RBZ were 14.3-15.2 at pH 6-9 and reduced at higher or lower pH. In conclusion, traditional organic co-solvents, pH-adjustment or complexation (with HP-beta-CD) approaches are unlikely to yield sufficient solubility for formulation of RBZ solutions for subcutaneous injection and novel approaches should be considered.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277026"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277026"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277026; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277026]").text(description); $(".js-view-count[data-work-id=111277026]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277026; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277026']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277026, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277026]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277026,"title":"Physicochemical Characterization of Ricobendazole: I. Solubility, Lipophilicity, and Ionization Characteristics","translated_title":"","metadata":{"abstract":"The physicochemical properties of ricobendazole (RBZ) were characterized using conventional methods. Solubility in some pharmaceutical solvents, pH-solubility, ionization properties, and lipophilicity are described. The solubility of RBZ in water is 62 mug/mL and very poor in common pharmaceutical solvents, for example, oils (\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.25 mg/mL in all the tested oils) or ethanol (1.2 mg/mL) and propylene glycol (2.6 mg/mL), and slightly higher in dipolar solvents, DMSO (16.5 mg/mL). U-shaped pH-solubility profile in aqueous solutions indicates RBZ is an ampholyte. pK(a) values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 for the basic group and 9.82 and 9.53 for the non-basic nitrogen, respectively. Combination of low pH and surfactant/co-solvent mixtures also improved solubility. RBZ formed a 1:1 complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a binding constant (K(1:1)) of 311/M1. Apparent partition coefficients of RBZ were 14.3-15.2 at pH 6-9 and reduced at higher or lower pH. In conclusion, traditional organic co-solvents, pH-adjustment or complexation (with HP-beta-CD) approaches are unlikely to yield sufficient solubility for formulation of RBZ solutions for subcutaneous injection and novel approaches should be considered.","publisher":"Elsevier BV","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Journal of Pharmaceutical Sciences"},"translated_abstract":"The physicochemical properties of ricobendazole (RBZ) were characterized using conventional methods. Solubility in some pharmaceutical solvents, pH-solubility, ionization properties, and lipophilicity are described. The solubility of RBZ in water is 62 mug/mL and very poor in common pharmaceutical solvents, for example, oils (\u0026amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.25 mg/mL in all the tested oils) or ethanol (1.2 mg/mL) and propylene glycol (2.6 mg/mL), and slightly higher in dipolar solvents, DMSO (16.5 mg/mL). U-shaped pH-solubility profile in aqueous solutions indicates RBZ is an ampholyte. pK(a) values measured by absorbance spectroscopy and pH solubility methods were 3.45 and 3.76 for the basic group and 9.82 and 9.53 for the non-basic nitrogen, respectively. Combination of low pH and surfactant/co-solvent mixtures also improved solubility. RBZ formed a 1:1 complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a binding constant (K(1:1)) of 311/M1. Apparent partition coefficients of RBZ were 14.3-15.2 at pH 6-9 and reduced at higher or lower pH. In conclusion, traditional organic co-solvents, pH-adjustment or complexation (with HP-beta-CD) approaches are unlikely to yield sufficient solubility for formulation of RBZ solutions for subcutaneous injection and novel approaches should be considered.","internal_url":"https://www.academia.edu/111277026/Physicochemical_Characterization_of_Ricobendazole_I_Solubility_Lipophilicity_and_Ionization_Characteristics","translated_internal_url":"","created_at":"2023-12-12T16:46:03.833-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Physicochemical_Characterization_of_Ricobendazole_I_Solubility_Lipophilicity_and_Ionization_Characteristics","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":428,"name":"Algorithms","url":"https://www.academia.edu/Documents/in/Algorithms"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":532,"name":"Physical Chemistry","url":"https://www.academia.edu/Documents/in/Physical_Chemistry"},{"id":23390,"name":"Pharmaceutical Chemistry","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Chemistry"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":52055,"name":"Lipids","url":"https://www.academia.edu/Documents/in/Lipids"},{"id":89956,"name":"Pharmaceutical Sciences","url":"https://www.academia.edu/Documents/in/Pharmaceutical_Sciences"},{"id":205584,"name":"Solubility","url":"https://www.academia.edu/Documents/in/Solubility"},{"id":206307,"name":"Albendazole","url":"https://www.academia.edu/Documents/in/Albendazole"},{"id":246560,"name":"High Pressure Liquid Chromatography","url":"https://www.academia.edu/Documents/in/High_Pressure_Liquid_Chromatography"},{"id":329196,"name":"Ionization","url":"https://www.academia.edu/Documents/in/Ionization"},{"id":498676,"name":"Lipophilicity","url":"https://www.academia.edu/Documents/in/Lipophilicity"},{"id":756431,"name":"log P","url":"https://www.academia.edu/Documents/in/log_P"},{"id":989646,"name":"Aqueous Solution","url":"https://www.academia.edu/Documents/in/Aqueous_Solution"},{"id":1137254,"name":"Hydrogen-Ion Concentration","url":"https://www.academia.edu/Documents/in/Hydrogen-Ion_Concentration"},{"id":1186482,"name":"Solvent","url":"https://www.academia.edu/Documents/in/Solvent"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980407,"url":"https://api.elsevier.com/content/article/PII:S0022354916317701?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277024"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277024/Synthesis_and_pharmacokinetics_of_strontium_fructose_1_6_diphosphate_Sr_FDP_as_a_potential_anti_osteoporosis_agent_in_intact_and_ovariectomized_rats"><img alt="Research paper thumbnail of Synthesis and pharmacokinetics of strontium fructose 1,6-diphosphate (Sr-FDP) as a potential anti-osteoporosis agent in intact and ovariectomized rats" class="work-thumbnail" src="https://attachments.academia-assets.com/108858250/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277024/Synthesis_and_pharmacokinetics_of_strontium_fructose_1_6_diphosphate_Sr_FDP_as_a_potential_anti_osteoporosis_agent_in_intact_and_ovariectomized_rats">Synthesis and pharmacokinetics of strontium fructose 1,6-diphosphate (Sr-FDP) as a potential anti-osteoporosis agent in intact and ovariectomized rats</a></div><div class="wp-workCard_item"><span>Journal of Inorganic Biochemistry</span><span>, 2011</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="dd18718fd4036dad7e51035128b09d6c" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858250,&quot;asset_id&quot;:111277024,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858250/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277024"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277024"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277024; 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The compound was characterized and confirmed with elemental analyses and spectroscopic (IR, NMR) methods. The pharmacokinetic profiles of Sr-FDP were investigated in Sprague-Dawley rats following oral administration at a dose of 110, 220, and 440 mg/kg respectively. Pharmacokinetic differences were also compared in intact rats and ovariectomized rats with and without estrogen supplement. Strontium concentrations in plasma, urine, tissue and feces were determined by graphite furnace atomic absorption spectroscopy (GFAAS). The results showed that Sr-FDP was absorbed rapidly with T max b 1 h in all the groups with AUC 0-∞ proportional to the oral dose. The pharmacokinetic profiles were characterized by long half-life, a large apparent volume of distribution. The highest Sr concentration was observed in the bone at 6 h, and the level of Sr decreased close to the baseline in heart, liver, spleen, lung, intestine, brain and kidney after 12 h. The cumulative amounts of Sr over 96 h were found to be~3% in urine, but~70% in feces suggesting that the parent drug was mainly excreted from the intestine. The C max and AUC 0-∞ of Sr-FDP in ovariectomized rats were significantly decreased compared to those in intact rats, and this trend was ameliorated by using 17-beta-estradiol (E 2) treatment in the ovariectomized rats.","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Journal of Inorganic Biochemistry","grobid_abstract_attachment_id":108858250},"translated_abstract":null,"internal_url":"https://www.academia.edu/111277024/Synthesis_and_pharmacokinetics_of_strontium_fructose_1_6_diphosphate_Sr_FDP_as_a_potential_anti_osteoporosis_agent_in_intact_and_ovariectomized_rats","translated_internal_url":"","created_at":"2023-12-12T16:46:02.952-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858250,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858250/thumbnails/1.jpg","file_name":"j.jinorgbio.2011.01.00120231213-1-tund90.pdf","download_url":"https://www.academia.edu/attachments/108858250/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Synthesis_and_pharmacokinetics_of_stront.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858250/j.jinorgbio.2011.01.00120231213-1-tund90-libre.pdf?1702428623=\u0026response-content-disposition=attachment%3B+filename%3DSynthesis_and_pharmacokinetics_of_stront.pdf\u0026Expires=1732823520\u0026Signature=R~mGAKRJ41MtyzN-08~z7KMCLJ4BSNH3GBlCDmGxCebqOWB6fqjfpF4Tl-vJex~XTP0MF8oAGr1XbnFWlvgGbkqRyVs22Xd~182cszHmNKoTF5JWzNigBdeFMD4coabcVLt1jXH3-NfuqQvfWE65jUgTx86xtpbdDG9f~pvOnxKTHvHRWBxHu7zVDgHV0TqTyrMCMjP698kGDLR7l~UDjN-HsYi0isX80JHEPOEe302JVgR6cmHljxPCqgW0~5Mo6y3HSVCluvv7cddtb2Rbu5pQuCk4~DhiHbep5cI~nyTPJwt3PHejxZ1VpJotb7ZPxwolFG6NU-~AK-Z7APxAQg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Synthesis_and_pharmacokinetics_of_strontium_fructose_1_6_diphosphate_Sr_FDP_as_a_potential_anti_osteoporosis_agent_in_intact_and_ovariectomized_rats","translated_slug":"","page_count":6,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858250,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858250/thumbnails/1.jpg","file_name":"j.jinorgbio.2011.01.00120231213-1-tund90.pdf","download_url":"https://www.academia.edu/attachments/108858250/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Synthesis_and_pharmacokinetics_of_stront.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858250/j.jinorgbio.2011.01.00120231213-1-tund90-libre.pdf?1702428623=\u0026response-content-disposition=attachment%3B+filename%3DSynthesis_and_pharmacokinetics_of_stront.pdf\u0026Expires=1732823520\u0026Signature=R~mGAKRJ41MtyzN-08~z7KMCLJ4BSNH3GBlCDmGxCebqOWB6fqjfpF4Tl-vJex~XTP0MF8oAGr1XbnFWlvgGbkqRyVs22Xd~182cszHmNKoTF5JWzNigBdeFMD4coabcVLt1jXH3-NfuqQvfWE65jUgTx86xtpbdDG9f~pvOnxKTHvHRWBxHu7zVDgHV0TqTyrMCMjP698kGDLR7l~UDjN-HsYi0isX80JHEPOEe302JVgR6cmHljxPCqgW0~5Mo6y3HSVCluvv7cddtb2Rbu5pQuCk4~DhiHbep5cI~nyTPJwt3PHejxZ1VpJotb7ZPxwolFG6NU-~AK-Z7APxAQg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":154,"name":"Endocrinology","url":"https://www.academia.edu/Documents/in/Endocrinology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":530,"name":"Inorganic Chemistry","url":"https://www.academia.edu/Documents/in/Inorganic_Chemistry"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":63997,"name":"Osteoporosis","url":"https://www.academia.edu/Documents/in/Osteoporosis"},{"id":65390,"name":"Internal Medicine","url":"https://www.academia.edu/Documents/in/Internal_Medicine"},{"id":78130,"name":"Strontium","url":"https://www.academia.edu/Documents/in/Strontium"},{"id":178360,"name":"Urine","url":"https://www.academia.edu/Documents/in/Urine"},{"id":235677,"name":"Behavioral Animal Models","url":"https://www.academia.edu/Documents/in/Behavioral_Animal_Models"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":702312,"name":"Atomic Absorption Spectroscopy","url":"https://www.academia.edu/Documents/in/Atomic_Absorption_Spectroscopy"},{"id":773664,"name":"Inorganic Biochemistry","url":"https://www.academia.edu/Documents/in/Inorganic_Biochemistry"},{"id":1993786,"name":"Cumulant","url":"https://www.academia.edu/Documents/in/Cumulant"},{"id":2053987,"name":"Ovariectomy","url":"https://www.academia.edu/Documents/in/Ovariectomy"},{"id":2229160,"name":"Ovariectomized Rat","url":"https://www.academia.edu/Documents/in/Ovariectomized_Rat"},{"id":2950651,"name":"Tissue distribution","url":"https://www.academia.edu/Documents/in/Tissue_distribution"}],"urls":[{"id":36980405,"url":"https://api.elsevier.com/content/article/PII:S016201341100002X?httpAccept=text/xml"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277022"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277022/Pre_formulation_and_chemical_stability_studies_of_penethamate_a_benzylpenicillin_ester_prodrug_in_aqueous_vehicles"><img alt="Research paper thumbnail of Pre-formulation and chemical stability studies of penethamate, a benzylpenicillin ester prodrug, in aqueous vehicles" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277022/Pre_formulation_and_chemical_stability_studies_of_penethamate_a_benzylpenicillin_ester_prodrug_in_aqueous_vehicles">Pre-formulation and chemical stability studies of penethamate, a benzylpenicillin ester prodrug, in aqueous vehicles</a></div><div class="wp-workCard_item"><span>Drug Development and Industrial Pharmacy</span><span>, 2011</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine m...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277022"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277022"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277022; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277022]").text(description); $(".js-view-count[data-work-id=111277022]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277022; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277022']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277022, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111277022]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277022,"title":"Pre-formulation and chemical stability studies of penethamate, a benzylpenicillin ester prodrug, in aqueous vehicles","translated_title":"","metadata":{"abstract":"Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.","publisher":"Informa UK Limited","publication_date":{"day":null,"month":null,"year":2011,"errors":{}},"publication_name":"Drug Development and Industrial Pharmacy"},"translated_abstract":"Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.","internal_url":"https://www.academia.edu/111277022/Pre_formulation_and_chemical_stability_studies_of_penethamate_a_benzylpenicillin_ester_prodrug_in_aqueous_vehicles","translated_internal_url":"","created_at":"2023-12-12T16:46:02.335-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Pre_formulation_and_chemical_stability_studies_of_penethamate_a_benzylpenicillin_ester_prodrug_in_aqueous_vehicles","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":2215,"name":"Water","url":"https://www.academia.edu/Documents/in/Water"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":13841,"name":"Drug development","url":"https://www.academia.edu/Documents/in/Drug_development"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":64461,"name":"Prodrugs","url":"https://www.academia.edu/Documents/in/Prodrugs"},{"id":133177,"name":"Temperature","url":"https://www.academia.edu/Documents/in/Temperature"},{"id":178352,"name":"Prodrug","url":"https://www.academia.edu/Documents/in/Prodrug"},{"id":205584,"name":"Solubility","url":"https://www.academia.edu/Documents/in/Solubility"},{"id":207059,"name":"Suspensions","url":"https://www.academia.edu/Documents/in/Suspensions"},{"id":376308,"name":"Buffers","url":"https://www.academia.edu/Documents/in/Buffers"},{"id":414692,"name":"Solutions","url":"https://www.academia.edu/Documents/in/Solutions"},{"id":989646,"name":"Aqueous Solution","url":"https://www.academia.edu/Documents/in/Aqueous_Solution"},{"id":1121353,"name":"Esters","url":"https://www.academia.edu/Documents/in/Esters"},{"id":1135766,"name":"Excipients","url":"https://www.academia.edu/Documents/in/Excipients"},{"id":1135814,"name":"Drug Stability","url":"https://www.academia.edu/Documents/in/Drug_Stability"},{"id":1186482,"name":"Solvent","url":"https://www.academia.edu/Documents/in/Solvent"},{"id":1745595,"name":"Solvents","url":"https://www.academia.edu/Documents/in/Solvents"},{"id":2298646,"name":"Penicillin G","url":"https://www.academia.edu/Documents/in/Penicillin_G"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980403,"url":"http://www.tandfonline.com/doi/pdf/10.3109/03639045.2011.590497"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111277020"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111277020/Gas_Chromatography_Time_Of_Flight_Mass_Spectrometry_Based_Metabolomic_Analysis_of_Human_Macrophages_Infected_byM_tuberculosis"><img alt="Research paper thumbnail of Gas Chromatography Time-Of-Flight Mass Spectrometry-Based Metabolomic Analysis of Human Macrophages Infected byM. tuberculosis" class="work-thumbnail" src="https://attachments.academia-assets.com/108858248/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111277020/Gas_Chromatography_Time_Of_Flight_Mass_Spectrometry_Based_Metabolomic_Analysis_of_Human_Macrophages_Infected_byM_tuberculosis">Gas Chromatography Time-Of-Flight Mass Spectrometry-Based Metabolomic Analysis of Human Macrophages Infected byM. tuberculosis</a></div><div class="wp-workCard_item"><span>Analytical Letters</span><span>, 2013</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="2f2a03c82eba5402e754a69ed593fbbd" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:108858248,&quot;asset_id&quot;:111277020,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/108858248/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111277020"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111277020"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111277020; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111277020]").text(description); $(".js-view-count[data-work-id=111277020]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111277020; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111277020']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111277020, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "2f2a03c82eba5402e754a69ed593fbbd" } } $('.js-work-strip[data-work-id=111277020]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111277020,"title":"Gas Chromatography Time-Of-Flight Mass Spectrometry-Based Metabolomic Analysis of Human Macrophages Infected byM. tuberculosis","translated_title":"","metadata":{"publisher":"Informa UK Limited","grobid_abstract":"In this study the spectrum storage rate, linearity of response, and detection limits of time-of-flight mass spectrometry in combination with capillary Ž. gas chromatography GC᎐TOF-MS were evaluated. TOF-MS was found to be a very powerful technique with limits of detection in the low pg range for Ž. Ž. organophosphorus pesticides OPPs, 1᎐6 pg , triazine herbicides 4᎐60 pg and Ž. polycyclic aromatic hydrocarbons 0.3᎐6 pg. Spectral information of good quality was obtained at spectrum storage rates of up to 500 Hz. For all analyte classes response concentration plots were linear in the range 2 pg᎐1 ng, which is very important in TOF-MS. GC᎐TOF-MS was applied to the determination of the above compound classes in various extracts, which were obtained by means of miniaturized extraction procedures. The analytes were extracted from aqueous Ž. samples surface water, tea and sediment into an organic solvent and 1 L of the extract was injected into the GC system using a split injector. One software tool, automated spectral peak deconvolution, turned out to be very valuable. It enabled calculation of spectra from overlapping peaks even if their retention times differed only three scans. Peaks were reported with their deconvoluted spectrum, the so-called peak true spectrum. In actual practice this means that peaks had to be separated for 0.3 or 0.15 s at a spectrum storage rate of 10 and 20 Hz, respectively. Three extraction procedures combined with GC᎐TOF-MS allowed the analysis of the microcontaminants at 0.1 grL in surface water, at 2 grL in tea, and at Ž. 0.01 mgrkg in sediment with a signal-to-noise ratio SrN of 10. In other words, relevant real-life detection limits can be obtained even under split injection conditions.","publication_date":{"day":null,"month":null,"year":2013,"errors":{}},"publication_name":"Analytical Letters","grobid_abstract_attachment_id":108858248},"translated_abstract":null,"internal_url":"https://www.academia.edu/111277020/Gas_Chromatography_Time_Of_Flight_Mass_Spectrometry_Based_Metabolomic_Analysis_of_Human_Macrophages_Infected_byM_tuberculosis","translated_internal_url":"","created_at":"2023-12-12T16:46:01.793-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":108858248,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858248/thumbnails/1.jpg","file_name":"28sici291520-667x2819991129113A93C6633A3Aaid-mcs43E3.0.co3B2-020231213-1-mfe7uo.pdf","download_url":"https://www.academia.edu/attachments/108858248/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Gas_Chromatography_Time_Of_Flight_Mass_S.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858248/28sici291520-667x2819991129113A93C6633A3Aaid-mcs43E3.0.co3B2-020231213-1-mfe7uo-libre.pdf?1702428625=\u0026response-content-disposition=attachment%3B+filename%3DGas_Chromatography_Time_Of_Flight_Mass_S.pdf\u0026Expires=1732823520\u0026Signature=bHs65ishhgbKDbYFxCnL91bvAYG-2dt4pBjZ21IMQK~XdE-MIPuKL89hGX6dEfslmBJQff7WrRvjc060JNV13qoGsBZBeSvFO3Q88vMSOlD3lSmFfsm4x3s4OhyHVSm7MXdSewpTjFAFNHpiC3sHcLVo0UHMhuddz8zWyVZPsseBmRrJ2MdSrjLOV~E-BJF3-I~9jqY1SJgYzrGptY07~Jk3-Cx0GTVjL~QyIYsYm-r-f33FKe7Chx6j2PSiWO63HSTNmjbZemhSvsJYCWWTgwACsU0Z5RXsmic5JlmKWvYqVo43INKxTwdWBcYb3PG6-RH~iNewjoZycX11WeSfuw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Gas_Chromatography_Time_Of_Flight_Mass_Spectrometry_Based_Metabolomic_Analysis_of_Human_Macrophages_Infected_byM_tuberculosis","translated_slug":"","page_count":13,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[{"id":108858248,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/108858248/thumbnails/1.jpg","file_name":"28sici291520-667x2819991129113A93C6633A3Aaid-mcs43E3.0.co3B2-020231213-1-mfe7uo.pdf","download_url":"https://www.academia.edu/attachments/108858248/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Gas_Chromatography_Time_Of_Flight_Mass_S.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/108858248/28sici291520-667x2819991129113A93C6633A3Aaid-mcs43E3.0.co3B2-020231213-1-mfe7uo-libre.pdf?1702428625=\u0026response-content-disposition=attachment%3B+filename%3DGas_Chromatography_Time_Of_Flight_Mass_S.pdf\u0026Expires=1732823520\u0026Signature=bHs65ishhgbKDbYFxCnL91bvAYG-2dt4pBjZ21IMQK~XdE-MIPuKL89hGX6dEfslmBJQff7WrRvjc060JNV13qoGsBZBeSvFO3Q88vMSOlD3lSmFfsm4x3s4OhyHVSm7MXdSewpTjFAFNHpiC3sHcLVo0UHMhuddz8zWyVZPsseBmRrJ2MdSrjLOV~E-BJF3-I~9jqY1SJgYzrGptY07~Jk3-Cx0GTVjL~QyIYsYm-r-f33FKe7Chx6j2PSiWO63HSTNmjbZemhSvsJYCWWTgwACsU0Z5RXsmic5JlmKWvYqVo43INKxTwdWBcYb3PG6-RH~iNewjoZycX11WeSfuw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":159,"name":"Microbiology","url":"https://www.academia.edu/Documents/in/Microbiology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":524,"name":"Analytical Chemistry","url":"https://www.academia.edu/Documents/in/Analytical_Chemistry"},{"id":4656,"name":"Chromatography","url":"https://www.academia.edu/Documents/in/Chromatography"},{"id":5769,"name":"Mass Spectrometry","url":"https://www.academia.edu/Documents/in/Mass_Spectrometry"},{"id":7802,"name":"Metabolomics","url":"https://www.academia.edu/Documents/in/Metabolomics"},{"id":9786,"name":"Proteomics","url":"https://www.academia.edu/Documents/in/Proteomics"},{"id":62235,"name":"Tuberculosis","url":"https://www.academia.edu/Documents/in/Tuberculosis"},{"id":68318,"name":"Mycobacterium tuberculosis","url":"https://www.academia.edu/Documents/in/Mycobacterium_tuberculosis"},{"id":764799,"name":"Metabolic pathway","url":"https://www.academia.edu/Documents/in/Metabolic_pathway"},{"id":1292327,"name":"Metabolome","url":"https://www.academia.edu/Documents/in/Metabolome"}],"urls":[{"id":36980401,"url":"http://www.tandfonline.com/doi/pdf/10.1080/00032719.2013.777924"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="111276916"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/111276916/Co_Delivery_Using_pH_Sensitive_Liposomes_to_Pancreatic_Cancer_Cells_the_Effects_of_Curcumin_on_Cellular_Concentration_and_Pharmacokinetics_of_Gemcitabine"><img alt="Research paper thumbnail of Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/111276916/Co_Delivery_Using_pH_Sensitive_Liposomes_to_Pancreatic_Cancer_Cells_the_Effects_of_Curcumin_on_Cellular_Concentration_and_Pharmacokinetics_of_Gemcitabine">Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine</a></div><div class="wp-workCard_item"><span>Pharmaceutical Research</span><span>, Jun 29, 2021</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">PURPOSE PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were inv...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">PURPOSE PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were investigated for the potential application in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) treatment. Curcumin was employed as an inhibitor of the efflux transporter, multidrug resistance protein 5 (MRP5) in PDAC cells. METHODS Liposomes were prepared with gemcitabine in the core and curcumin in the bilayers. The effects of curcumin on pH-sensitivity and &amp;#39;endosome escape&amp;#39; of PSL with different PEGylation were investigated using a calcein self-quench assay. The effects of curcumin on intracellular gemcitabine concentrations, and cytotoxicity to a MIA PaCa-2 PDAC cell line was evaluated. The pharmacokinetics were investigated in rats following intravenous injection. RESULTS The addition of curcumin to the PSL bilayers (0.2-1 mol%)slightly decreased the pH-sensitivity of PSL, but to a less extent than PEGylation (0-5 mol%). Co-treatment with curcumin increased gemcitabine cellular accumulation in a concentration-dependent manner, and resulted in synergistic cytotoxicity towards MIA PaCa-2cells.Both these effects were augmented by the use of PSL, particularly when the two drugs were co-loaded in PSL. In rats, the dual-drug loaded PSL produced significantly reduced (p &amp;lt; 0.05) plasma clearance (CL) and volume of distribution (Vd) for both drugs, alongside 3 to 4-fold increases in the area-under-the-concentration-time curves compared to the free drugs. Additionally, curcumin slightly increase the plasma concentrations of gemcitabine possibly also via the MRP5 inhibition effect. CONCLUSION Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration thus cytotoxicity to MIA PaCa-2 cells but also significantly improved the pharmacokinetic profiles for both drugs. Graphical Abstract.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="111276916"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="111276916"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 111276916; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=111276916]").text(description); $(".js-view-count[data-work-id=111276916]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 111276916; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='111276916']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 111276916, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=111276916]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":111276916,"title":"Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine","translated_title":"","metadata":{"abstract":"PURPOSE PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were investigated for the potential application in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) treatment. Curcumin was employed as an inhibitor of the efflux transporter, multidrug resistance protein 5 (MRP5) in PDAC cells. METHODS Liposomes were prepared with gemcitabine in the core and curcumin in the bilayers. The effects of curcumin on pH-sensitivity and \u0026#39;endosome escape\u0026#39; of PSL with different PEGylation were investigated using a calcein self-quench assay. The effects of curcumin on intracellular gemcitabine concentrations, and cytotoxicity to a MIA PaCa-2 PDAC cell line was evaluated. The pharmacokinetics were investigated in rats following intravenous injection. RESULTS The addition of curcumin to the PSL bilayers (0.2-1 mol%)slightly decreased the pH-sensitivity of PSL, but to a less extent than PEGylation (0-5 mol%). Co-treatment with curcumin increased gemcitabine cellular accumulation in a concentration-dependent manner, and resulted in synergistic cytotoxicity towards MIA PaCa-2cells.Both these effects were augmented by the use of PSL, particularly when the two drugs were co-loaded in PSL. In rats, the dual-drug loaded PSL produced significantly reduced (p \u0026lt; 0.05) plasma clearance (CL) and volume of distribution (Vd) for both drugs, alongside 3 to 4-fold increases in the area-under-the-concentration-time curves compared to the free drugs. Additionally, curcumin slightly increase the plasma concentrations of gemcitabine possibly also via the MRP5 inhibition effect. CONCLUSION Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration thus cytotoxicity to MIA PaCa-2 cells but also significantly improved the pharmacokinetic profiles for both drugs. Graphical Abstract.","publisher":"Springer Science+Business Media","publication_date":{"day":29,"month":6,"year":2021,"errors":{}},"publication_name":"Pharmaceutical Research"},"translated_abstract":"PURPOSE PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were investigated for the potential application in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) treatment. Curcumin was employed as an inhibitor of the efflux transporter, multidrug resistance protein 5 (MRP5) in PDAC cells. METHODS Liposomes were prepared with gemcitabine in the core and curcumin in the bilayers. The effects of curcumin on pH-sensitivity and \u0026#39;endosome escape\u0026#39; of PSL with different PEGylation were investigated using a calcein self-quench assay. The effects of curcumin on intracellular gemcitabine concentrations, and cytotoxicity to a MIA PaCa-2 PDAC cell line was evaluated. The pharmacokinetics were investigated in rats following intravenous injection. RESULTS The addition of curcumin to the PSL bilayers (0.2-1 mol%)slightly decreased the pH-sensitivity of PSL, but to a less extent than PEGylation (0-5 mol%). Co-treatment with curcumin increased gemcitabine cellular accumulation in a concentration-dependent manner, and resulted in synergistic cytotoxicity towards MIA PaCa-2cells.Both these effects were augmented by the use of PSL, particularly when the two drugs were co-loaded in PSL. In rats, the dual-drug loaded PSL produced significantly reduced (p \u0026lt; 0.05) plasma clearance (CL) and volume of distribution (Vd) for both drugs, alongside 3 to 4-fold increases in the area-under-the-concentration-time curves compared to the free drugs. Additionally, curcumin slightly increase the plasma concentrations of gemcitabine possibly also via the MRP5 inhibition effect. CONCLUSION Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration thus cytotoxicity to MIA PaCa-2 cells but also significantly improved the pharmacokinetic profiles for both drugs. Graphical Abstract.","internal_url":"https://www.academia.edu/111276916/Co_Delivery_Using_pH_Sensitive_Liposomes_to_Pancreatic_Cancer_Cells_the_Effects_of_Curcumin_on_Cellular_Concentration_and_Pharmacokinetics_of_Gemcitabine","translated_internal_url":"","created_at":"2023-12-12T16:44:14.199-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Co_Delivery_Using_pH_Sensitive_Liposomes_to_Pancreatic_Cancer_Cells_the_Effects_of_Curcumin_on_Cellular_Concentration_and_Pharmacokinetics_of_Gemcitabine","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":140,"name":"Pharmacology","url":"https://www.academia.edu/Documents/in/Pharmacology"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":11111,"name":"Pharmacokinetics","url":"https://www.academia.edu/Documents/in/Pharmacokinetics"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":93232,"name":"Curcumin","url":"https://www.academia.edu/Documents/in/Curcumin"},{"id":95655,"name":"Pharmaceutical","url":"https://www.academia.edu/Documents/in/Pharmaceutical"},{"id":129181,"name":"PEGylation","url":"https://www.academia.edu/Documents/in/PEGylation"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[{"id":36980313,"url":"https://doi.org/10.1007/s11095-021-03072-2"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="105558650"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/105558650/Niosomal_Nanocarriers_for_Enhanced_Dermal_Delivery_of_Epigallocatechin_Gallate_for_Protection_against_Oxidative_Stress_of_the_Skin"><img alt="Research paper thumbnail of Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin" class="work-thumbnail" src="https://attachments.academia-assets.com/104978750/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/105558650/Niosomal_Nanocarriers_for_Enhanced_Dermal_Delivery_of_Epigallocatechin_Gallate_for_Protection_against_Oxidative_Stress_of_the_Skin">Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin</a></div><div class="wp-workCard_item"><span>Pharmaceutics</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highe...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of −45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c884461427f53f3443dcbab5bab3a97d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{&quot;attachment_id&quot;:104978750,&quot;asset_id&quot;:105558650,&quot;asset_type&quot;:&quot;Work&quot;,&quot;button_location&quot;:&quot;profile&quot;}" href="https://www.academia.edu/attachments/104978750/download_file?st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&st=MTczMjgxOTkyMCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="105558650"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="105558650"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 105558650; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=105558650]").text(description); $(".js-view-count[data-work-id=105558650]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 105558650; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='105558650']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 105558650, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "c884461427f53f3443dcbab5bab3a97d" } } $('.js-work-strip[data-work-id=105558650]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":105558650,"title":"Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin","translated_title":"","metadata":{"abstract":"Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of −45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. 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The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of −45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="105558649"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/105558649/The_Preparation_of_High_content_Gemcitabine_pH_Sensitive_Liposomes_and_Evaluation_of_their_Cytotoxicity_to_Drug_Resistant_Pancreatic_Cancer_Cells"><img alt="Research paper thumbnail of The Preparation of High-content Gemcitabine pH Sensitive Liposomes and Evaluation of their Cytotoxicity to Drug Resistant Pancreatic Cancer Cells" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/105558649/The_Preparation_of_High_content_Gemcitabine_pH_Sensitive_Liposomes_and_Evaluation_of_their_Cytotoxicity_to_Drug_Resistant_Pancreatic_Cancer_Cells">The Preparation of High-content Gemcitabine pH Sensitive Liposomes and Evaluation of their Cytotoxicity to Drug Resistant Pancreatic Cancer Cells</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">SUMMARY Gemcitabine containing pH sensitive liposomes (PSL) has been prepared using a Small Volum...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">SUMMARY Gemcitabine containing pH sensitive liposomes (PSL) has been prepared using a Small Volume Incubation (SVI) method. The entrapment efficiency (EE) and drug loading (DL) were 29.5 ± 0.2% and 4.2 ± 0.2%, a respective 7and 70-fold increase compared to the thin film hydration extrusion (TFHE) method. The particle size and zeta potential were 146 ± 2 nm and -26.4 ± 2.0 mV. The gemcitabine PSL showed significantly enhanced cytotoxicity than free gemcitabine solution and gemcitabine non-pH-sensitive liposomes (NPSL) to pancreatic cancer cells. INTRODUCTION Over-expression of multidrug resistance proteins (MRP) in pancreatic cancer cells confers resistance to the major first-line drug, gemcitabine, due to MRP-mediated efflux of gemcitabine and/or its active metabolite[1]. This has posed a challenge in efficient intracellular delivery of gemcitabine to the nucleus of the cancer cells. The PSL, capable of endosomal escape after endocytosis, appear to be a suitable carrier system for d...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="105558649"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="105558649"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 105558649; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=105558649]").text(description); $(".js-view-count[data-work-id=105558649]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 105558649; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='105558649']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 105558649, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=105558649]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":105558649,"title":"The Preparation of High-content Gemcitabine pH Sensitive Liposomes and Evaluation of their Cytotoxicity to Drug Resistant Pancreatic Cancer Cells","translated_title":"","metadata":{"abstract":"SUMMARY Gemcitabine containing pH sensitive liposomes (PSL) has been prepared using a Small Volume Incubation (SVI) method. The entrapment efficiency (EE) and drug loading (DL) were 29.5 ± 0.2% and 4.2 ± 0.2%, a respective 7and 70-fold increase compared to the thin film hydration extrusion (TFHE) method. The particle size and zeta potential were 146 ± 2 nm and -26.4 ± 2.0 mV. The gemcitabine PSL showed significantly enhanced cytotoxicity than free gemcitabine solution and gemcitabine non-pH-sensitive liposomes (NPSL) to pancreatic cancer cells. INTRODUCTION Over-expression of multidrug resistance proteins (MRP) in pancreatic cancer cells confers resistance to the major first-line drug, gemcitabine, due to MRP-mediated efflux of gemcitabine and/or its active metabolite[1]. This has posed a challenge in efficient intracellular delivery of gemcitabine to the nucleus of the cancer cells. The PSL, capable of endosomal escape after endocytosis, appear to be a suitable carrier system for d...","publication_date":{"day":null,"month":null,"year":2014,"errors":{}}},"translated_abstract":"SUMMARY Gemcitabine containing pH sensitive liposomes (PSL) has been prepared using a Small Volume Incubation (SVI) method. The entrapment efficiency (EE) and drug loading (DL) were 29.5 ± 0.2% and 4.2 ± 0.2%, a respective 7and 70-fold increase compared to the thin film hydration extrusion (TFHE) method. The particle size and zeta potential were 146 ± 2 nm and -26.4 ± 2.0 mV. The gemcitabine PSL showed significantly enhanced cytotoxicity than free gemcitabine solution and gemcitabine non-pH-sensitive liposomes (NPSL) to pancreatic cancer cells. INTRODUCTION Over-expression of multidrug resistance proteins (MRP) in pancreatic cancer cells confers resistance to the major first-line drug, gemcitabine, due to MRP-mediated efflux of gemcitabine and/or its active metabolite[1]. This has posed a challenge in efficient intracellular delivery of gemcitabine to the nucleus of the cancer cells. The PSL, capable of endosomal escape after endocytosis, appear to be a suitable carrier system for d...","internal_url":"https://www.academia.edu/105558649/The_Preparation_of_High_content_Gemcitabine_pH_Sensitive_Liposomes_and_Evaluation_of_their_Cytotoxicity_to_Drug_Resistant_Pancreatic_Cancer_Cells","translated_internal_url":"","created_at":"2023-08-13T17:19:24.626-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":53169921,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"The_Preparation_of_High_content_Gemcitabine_pH_Sensitive_Liposomes_and_Evaluation_of_their_Cytotoxicity_to_Drug_Resistant_Pancreatic_Cancer_Cells","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":53169921,"first_name":"Zimei","middle_initials":null,"last_name":"Wu","page_name":"ZimeiWu","domain_name":"independent","created_at":"2016-09-08T20:13:33.283-07:00","display_name":"Zimei Wu","url":"https://independent.academia.edu/ZimeiWu"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":6021,"name":"Cancer","url":"https://www.academia.edu/Documents/in/Cancer"},{"id":22050,"name":"Cytotoxicity","url":"https://www.academia.edu/Documents/in/Cytotoxicity"},{"id":26623,"name":"Pancreatic Cancer","url":"https://www.academia.edu/Documents/in/Pancreatic_Cancer"},{"id":42135,"name":"Drug","url":"https://www.academia.edu/Documents/in/Drug"},{"id":183266,"name":"Liposome","url":"https://www.academia.edu/Documents/in/Liposome"},{"id":1266879,"name":"Gemcitabine","url":"https://www.academia.edu/Documents/in/Gemcitabine"}],"urls":[{"id":33405269,"url":"http://www.controlledreleasesociety.org/meetings/Documents/2014Abstracts/10391.pdf"}]}, dispatcherData: dispatcherData }); 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