Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells

Sidi Yang,1,2 Yufei Chen,1,2 Kaien Gu,1,2 Alicia Dash,1,2 Casey L Sayre,1 Neal M Davies,1 Emmanuel A Ho1,2 1Faculty of Pharmacy, 2Laboratory for Drug Delivery and Biomaterials, University of Manitoba, Winnipeg, MB, Canada Abstract: The goal of this study was to develop and characterize an intravagin...

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Autores principales:	Yang S, Chen Y, Gu K, Dash A, Sayre CL, Davies NM, Ho EA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9b273b3d39514f8baa565e2d66c84ab6
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spelling	oai:doaj.org-article:9b273b3d39514f8baa565e2d66c84ab62021-12-02T02:38:18ZNovel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells1176-91141178-2013https://doaj.org/article/9b273b3d39514f8baa565e2d66c84ab62013-08-01T00:00:00Zhttp://www.dovepress.com/novel-intravaginal-nanomedicine-for-the-targeted-delivery-of-saquinavi-a13955https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Sidi Yang,1,2 Yufei Chen,1,2 Kaien Gu,1,2 Alicia Dash,1,2 Casey L Sayre,1 Neal M Davies,1 Emmanuel A Ho1,2 1Faculty of Pharmacy, 2Laboratory for Drug Delivery and Biomaterials, University of Manitoba, Winnipeg, MB, Canada Abstract: The goal of this study was to develop and characterize an intravaginal nanomedicine for the active targeted delivery of saquinavir (SQV) to CD4+ immune cells as a potential strategy to prevent or reduce HIV infection. The nanomedicine was formulated into a vaginal gel to provide ease in self-administration and to enhance retention within the vaginal tract. SQV-encapsulated nanoparticles (SQV-NPs) were prepared from poly(lactic-co-glycolic acid)(PLGA) and conjugated to antihuman anti-CD4 antibody. Antibody-conjugated SQV-NPs (Ab-SQV-NPs) had an encapsulation efficiency (EE%) of 74.4% ± 3.7% and an antibody conjugation efficiency (ACE%) of 80.95% ± 1.10%. Over 50% of total loaded SQV was released from NPs over 3 days. NPs were rapidly taken up by Sup-T1 cells, with more than a twofold increase in the intracellular levels of SQV when delivered by Ab-SQV-NPs in comparison to controls 1 hour post-treatment. No cytotoxicity was observed when vaginal epithelial cells were treated for 24 hours with drug-free Ab-NPs (1,000 µg/mL), 1% HEC placebo gel (200 mg/mL), or 1% HEC gel loaded with drug-free Ab-NPs (5 mg NPs/g gel, 200 mg/mL of gel mixture). Overall, we described an intravaginal nanomedicine that is nontoxic and can specifically deliver SQV into CD4+ immune cells. This platform may demonstrate potential utility in its application as postexposure prophylaxis for the treatment or reduction of HIV infection, but further studies are required. Keywords: nanoparticles, saquinavir, antibody conjugation, intravaginal gel, HIV/AIDS, microbicideYang SChen YGu KDash ASayre CLDavies NMHo EADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2847-2858 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Yang S Chen Y Gu K Dash A Sayre CL Davies NM Ho EA Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells
description	Sidi Yang,1,2 Yufei Chen,1,2 Kaien Gu,1,2 Alicia Dash,1,2 Casey L Sayre,1 Neal M Davies,1 Emmanuel A Ho1,2 1Faculty of Pharmacy, 2Laboratory for Drug Delivery and Biomaterials, University of Manitoba, Winnipeg, MB, Canada Abstract: The goal of this study was to develop and characterize an intravaginal nanomedicine for the active targeted delivery of saquinavir (SQV) to CD4+ immune cells as a potential strategy to prevent or reduce HIV infection. The nanomedicine was formulated into a vaginal gel to provide ease in self-administration and to enhance retention within the vaginal tract. SQV-encapsulated nanoparticles (SQV-NPs) were prepared from poly(lactic-co-glycolic acid)(PLGA) and conjugated to antihuman anti-CD4 antibody. Antibody-conjugated SQV-NPs (Ab-SQV-NPs) had an encapsulation efficiency (EE%) of 74.4% ± 3.7% and an antibody conjugation efficiency (ACE%) of 80.95% ± 1.10%. Over 50% of total loaded SQV was released from NPs over 3 days. NPs were rapidly taken up by Sup-T1 cells, with more than a twofold increase in the intracellular levels of SQV when delivered by Ab-SQV-NPs in comparison to controls 1 hour post-treatment. No cytotoxicity was observed when vaginal epithelial cells were treated for 24 hours with drug-free Ab-NPs (1,000 µg/mL), 1% HEC placebo gel (200 mg/mL), or 1% HEC gel loaded with drug-free Ab-NPs (5 mg NPs/g gel, 200 mg/mL of gel mixture). Overall, we described an intravaginal nanomedicine that is nontoxic and can specifically deliver SQV into CD4+ immune cells. This platform may demonstrate potential utility in its application as postexposure prophylaxis for the treatment or reduction of HIV infection, but further studies are required. Keywords: nanoparticles, saquinavir, antibody conjugation, intravaginal gel, HIV/AIDS, microbicide
format	article
author	Yang S Chen Y Gu K Dash A Sayre CL Davies NM Ho EA
author_facet	Yang S Chen Y Gu K Dash A Sayre CL Davies NM Ho EA
author_sort	Yang S
title	Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells
title_short	Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells
title_full	Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells
title_fullStr	Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells
title_full_unstemmed	Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells
title_sort	novel intravaginal nanomedicine for the targeted delivery of saquinavir to cd4+ immune cells
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/9b273b3d39514f8baa565e2d66c84ab6
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Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells

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