Rational development of liposomal hydrogels: A strategy for topical vaginal antiretroviral drug delivery in the context of HIV prevention
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/61472 |
Resumo: | 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 (<i>J</i><sub>ss</sub> = 9.9 μg·cm<sup>−2</sup>·h<sup>−1</sup>). 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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Rational development of liposomal hydrogels: A strategy for topical vaginal antiretroviral drug delivery in the context of HIV preventiondrug releaseemtricitabinehydrogelsliposomesliposomesmicrobicidesnanomedicinetenofovir disoproxil fumaratetopical PrEPScience & TechnologyHIV/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 (<i>J</i><sub>ss</sub> = 9.9 μg·cm<sup>−2</sup>·h<sup>−1</sup>). 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.Funding for this work was provided by Fundação para a Ciência e Tecnologia (FCT) in the framework of the Strategic Funding UID/FIS/04650/2019 and in the ambit of the project POCI-01-0145-FEDER-032651 and PTDC/ NAN-MAT/326512017, co-financed by the European Regional Development Fund (ERDF), through COMPETE 2020, under Portugal 2020, and FCT I.P. This work was also supported by the strategic program UID/BIA/04050/2019 and project ERA-IB-2-6/0004/2014 funded by national Portuguese funds through FCT I.P. M. Lúcio thanks FCT and ERDF for doctoral position Ref. CTTI-150/18-CF(1) in the ambit of the project CONCERT (POCI-01-0145-FEDER-032651 and PTDC/NAN-MAT/326512017). This work was further supported by Institute for Research and Innovation in Health Sciences (UID/BIM/04293/2019), by Programa Gilead GÉNESE, Gilead Portugal (refs. PGG/046/2015 and PGG/002/2016), and by CEB (UID/BIO/04469/2019).Multidisciplinary Digital Publishing InstituteUniversidade do MinhoFaria, Maria J.Machado, RaulRibeiro, ArturGonçalves, HugoReal Oliveira, M. Elisabete C.D.Viseu, T. M. R.das Neves, JoséLúcio, M.2019-09-182019-09-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/61472engFaria, M.J.; Machado, R.; Ribeiro, A.; Gonçalves, H.; Real Oliveira, M.E.C.D.; Viseu, T.; das Neves, J.; Lúcio, M. Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention. Pharmaceutics. 2019, 11, 485.1999-492310.3390/pharmaceutics11090485https://www.mdpi.com/1999-4923/11/9/485info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:33:47Zoai:repositorium.sdum.uminho.pt:1822/61472Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:29:21.872431Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
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 |
spellingShingle |
Rational development of liposomal hydrogels: A strategy for topical vaginal antiretroviral drug delivery in the context of HIV prevention Faria, Maria J. drug release emtricitabine hydrogels liposomes liposomes microbicides nanomedicine tenofovir disoproxil fumarate topical PrEP Science & Technology |
title_short |
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_sort |
Rational development of liposomal hydrogels: A strategy for topical vaginal antiretroviral drug delivery in the context of HIV prevention |
author |
Faria, Maria J. |
author_facet |
Faria, Maria J. Machado, Raul Ribeiro, Artur Gonçalves, Hugo Real Oliveira, M. Elisabete C.D. Viseu, T. M. R. das Neves, José Lúcio, M. |
author_role |
author |
author2 |
Machado, Raul Ribeiro, Artur Gonçalves, Hugo Real Oliveira, M. Elisabete C.D. Viseu, T. M. R. das Neves, José Lúcio, M. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Faria, Maria J. Machado, Raul Ribeiro, Artur Gonçalves, Hugo Real Oliveira, M. Elisabete C.D. Viseu, T. M. R. das Neves, José Lúcio, M. |
dc.subject.por.fl_str_mv |
drug release emtricitabine hydrogels liposomes liposomes microbicides nanomedicine tenofovir disoproxil fumarate topical PrEP Science & Technology |
topic |
drug release emtricitabine hydrogels liposomes liposomes microbicides nanomedicine tenofovir disoproxil fumarate topical PrEP Science & Technology |
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 (<i>J</i><sub>ss</sub> = 9.9 μg·cm<sup>−2</sup>·h<sup>−1</sup>). 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. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-09-18 2019-09-18T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/61472 |
url |
http://hdl.handle.net/1822/61472 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Faria, M.J.; Machado, R.; Ribeiro, A.; Gonçalves, H.; Real Oliveira, M.E.C.D.; Viseu, T.; das Neves, J.; Lúcio, M. Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention. Pharmaceutics. 2019, 11, 485. 1999-4923 10.3390/pharmaceutics11090485 https://www.mdpi.com/1999-4923/11/9/485 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
dc.source.none.fl_str_mv |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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