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Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices

PURPOSE: Use of coital-dependent products to prevent HIV-1 transmission has resulted in mixed success. We hypothesize that incorporation of antiviral drug candidates into a novel controlled delivery system will prolong their activity, making their use coital independent, thus increasing their chance...

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Autores principales: Gunaseelan, Simi, Gallay, Philippe A., Bobardt, Michael D., Dezzutti, Charlene S., Esch, Timothy, Maskiewicz, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473190/
https://www.ncbi.nlm.nih.gov/pubmed/22736232
http://dx.doi.org/10.1007/s11095-012-0811-8
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author Gunaseelan, Simi
Gallay, Philippe A.
Bobardt, Michael D.
Dezzutti, Charlene S.
Esch, Timothy
Maskiewicz, Richard
author_facet Gunaseelan, Simi
Gallay, Philippe A.
Bobardt, Michael D.
Dezzutti, Charlene S.
Esch, Timothy
Maskiewicz, Richard
author_sort Gunaseelan, Simi
collection PubMed
description PURPOSE: Use of coital-dependent products to prevent HIV-1 transmission has resulted in mixed success. We hypothesize that incorporation of antiviral drug candidates into a novel controlled delivery system will prolong their activity, making their use coital independent, thus increasing their chance of prophylactic success. METHODS: Tenofovir, emtricitabine, and C5A peptide HIV microbicides were mechanically incorporated into matrices comprising a series of subliming solids. Matrix sublimation rates and drug release rates were measured in three in vitro and one in vivo environments intended to model human vaginal interior. Antiviral activity studies evaluating matrix incorporated microbicides were performed using in vitro cell cultures and human ectocervical explants. RESULTS: Drug release rates were identical to matrix sublimation rates, and were zero order. Differences in matrix material sublimation enthalpies determined drug release and matrix erosion rates in a thermodynamically definable manner, in vitro and in vivo. Durations of release ranging from several days to several months were readily achieved. Prolonged duration of anti HIV-1 activity was shown for matrix incorporated microbicides, using ectocervical explant and cell culture models of HIV-1 infection. CONCLUSION: Subliming solid matrices show promise as a delivery system providing multi month intravaginal release of a wide range of HIV-1 microbicides.
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spelling pubmed-34731902012-10-17 Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices Gunaseelan, Simi Gallay, Philippe A. Bobardt, Michael D. Dezzutti, Charlene S. Esch, Timothy Maskiewicz, Richard Pharm Res Research Paper PURPOSE: Use of coital-dependent products to prevent HIV-1 transmission has resulted in mixed success. We hypothesize that incorporation of antiviral drug candidates into a novel controlled delivery system will prolong their activity, making their use coital independent, thus increasing their chance of prophylactic success. METHODS: Tenofovir, emtricitabine, and C5A peptide HIV microbicides were mechanically incorporated into matrices comprising a series of subliming solids. Matrix sublimation rates and drug release rates were measured in three in vitro and one in vivo environments intended to model human vaginal interior. Antiviral activity studies evaluating matrix incorporated microbicides were performed using in vitro cell cultures and human ectocervical explants. RESULTS: Drug release rates were identical to matrix sublimation rates, and were zero order. Differences in matrix material sublimation enthalpies determined drug release and matrix erosion rates in a thermodynamically definable manner, in vitro and in vivo. Durations of release ranging from several days to several months were readily achieved. Prolonged duration of anti HIV-1 activity was shown for matrix incorporated microbicides, using ectocervical explant and cell culture models of HIV-1 infection. CONCLUSION: Subliming solid matrices show promise as a delivery system providing multi month intravaginal release of a wide range of HIV-1 microbicides. Springer US 2012-06-27 2012 /pmc/articles/PMC3473190/ /pubmed/22736232 http://dx.doi.org/10.1007/s11095-012-0811-8 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Research Paper
Gunaseelan, Simi
Gallay, Philippe A.
Bobardt, Michael D.
Dezzutti, Charlene S.
Esch, Timothy
Maskiewicz, Richard
Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices
title Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices
title_full Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices
title_fullStr Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices
title_full_unstemmed Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices
title_short Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices
title_sort sustained local delivery of structurally diverse hiv-1 microbicides released from sublimation enthalpy controlled matrices
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473190/
https://www.ncbi.nlm.nih.gov/pubmed/22736232
http://dx.doi.org/10.1007/s11095-012-0811-8
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