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Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention

HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evalu...

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Autores principales: Faria, Maria J., Machado, Raul, Ribeiro, Artur, Gonçalves, Hugo, Real Oliveira, Maria Elisabete C. D., Viseu, Teresa, das Neves, José, Lúcio, Marlene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781289/
https://www.ncbi.nlm.nih.gov/pubmed/31540519
http://dx.doi.org/10.3390/pharmaceutics11090485
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author Faria, Maria J.
Machado, Raul
Ribeiro, Artur
Gonçalves, Hugo
Real Oliveira, Maria Elisabete C. D.
Viseu, Teresa
das Neves, José
Lúcio, Marlene
author_facet Faria, Maria J.
Machado, Raul
Ribeiro, Artur
Gonçalves, Hugo
Real Oliveira, Maria Elisabete C. D.
Viseu, Teresa
das Neves, José
Lúcio, Marlene
author_sort Faria, Maria J.
collection PubMed
description HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evaluate the physicochemical characteristics of both drugs, and to study their biophysical impact in lipid model systems. Results from these pre-formulation studies defined hydrogels as adequate vehicles to incorporate TDF-loaded liposomes and FTC. After studying interactions with mucin, zwitterionic liposomes with a mean diameter of 134 ± 13 nm, an encapsulation TDF efficiency of approximately 84%, and a transition temperature of 41 °C were selected. The chosen liposomal formulation was non-cytotoxic to HEC-1-A and CaSki cells, and was able to favor TDF permeation across polysulfone membranes (J(ss) = 9.9 μg·cm(−2)·h(−1)). After the incorporation of TDF-loaded liposomes and FTC in carbomer hydrogels, the drug release profile was sustained over time, reaching around 60% for both drugs within 3–6 h, and best fitting the Weibull model. Moreover, liposomal hydrogels featured pseudoplastic profiles that were deemed suitable for topical application. Overall, the proposed liposomal hydrogels may constitute a promising formulation for the vaginal co-delivery of TDF/FTC.
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spelling pubmed-67812892019-10-30 Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention Faria, Maria J. Machado, Raul Ribeiro, Artur Gonçalves, Hugo Real Oliveira, Maria Elisabete C. D. Viseu, Teresa das Neves, José Lúcio, Marlene Pharmaceutics Article HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evaluate the physicochemical characteristics of both drugs, and to study their biophysical impact in lipid model systems. Results from these pre-formulation studies defined hydrogels as adequate vehicles to incorporate TDF-loaded liposomes and FTC. After studying interactions with mucin, zwitterionic liposomes with a mean diameter of 134 ± 13 nm, an encapsulation TDF efficiency of approximately 84%, and a transition temperature of 41 °C were selected. The chosen liposomal formulation was non-cytotoxic to HEC-1-A and CaSki cells, and was able to favor TDF permeation across polysulfone membranes (J(ss) = 9.9 μg·cm(−2)·h(−1)). After the incorporation of TDF-loaded liposomes and FTC in carbomer hydrogels, the drug release profile was sustained over time, reaching around 60% for both drugs within 3–6 h, and best fitting the Weibull model. Moreover, liposomal hydrogels featured pseudoplastic profiles that were deemed suitable for topical application. Overall, the proposed liposomal hydrogels may constitute a promising formulation for the vaginal co-delivery of TDF/FTC. MDPI 2019-09-18 /pmc/articles/PMC6781289/ /pubmed/31540519 http://dx.doi.org/10.3390/pharmaceutics11090485 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Faria, Maria J.
Machado, Raul
Ribeiro, Artur
Gonçalves, Hugo
Real Oliveira, Maria Elisabete C. D.
Viseu, Teresa
das Neves, José
Lúcio, Marlene
Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention
title Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention
title_full Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention
title_fullStr Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention
title_full_unstemmed Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention
title_short Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention
title_sort rational development of liposomal hydrogels: a strategy for topical vaginal antiretroviral drug delivery in the context of hiv prevention
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781289/
https://www.ncbi.nlm.nih.gov/pubmed/31540519
http://dx.doi.org/10.3390/pharmaceutics11090485
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