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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 \u00b1 13 nm, an encapsulation TDF efficiency of approximately 84%, and a transition temperature of 41 \u00b0C 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 (Jss = 9.9 \u03bcg\u00b7cm\u22122\u00b7h\u22121). 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\u20136 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics11090485","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T11:01:15Z","timestamp":1568804475000},"page":"485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention"],"prefix":"10.3390","volume":"11","author":[{"given":"Maria J.","family":"Faria","sequence":"first","affiliation":[{"name":"CF-UM-UP\u2014Centro de F\u00edsica das Universidades do Minho e Porto, Departamento de F\u00edsica da Universidade do Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-9945","authenticated-orcid":false,"given":"Raul","family":"Machado","sequence":"additional","affiliation":[{"name":"CBMA\u2014Centro de Biologia Molecular e Ambiental, Departamento de Biologia, Universidade do Minho, 4710-057 Braga, Portugal"},{"name":"IB-S\u2014Institute of Science and Innovation for Bio-Sustainability, Universidade do Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3298-5564","authenticated-orcid":false,"given":"Artur","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"CEB\u2014Centro de Engenharia Biol\u00f3gica, Universidade do Minho, 4710-057 Braga, Portugal"}]},{"given":"Hugo","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Paralab, SA, 4420-392 Valbom, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-8172","authenticated-orcid":false,"given":"Maria Elisabete C. D.","family":"Real Oliveira","sequence":"additional","affiliation":[{"name":"CF-UM-UP\u2014Centro de F\u00edsica das Universidades do Minho e Porto, Departamento de F\u00edsica da Universidade do Minho, 4710-057 Braga, Portugal"}]},{"given":"Teresa","family":"Viseu","sequence":"additional","affiliation":[{"name":"CF-UM-UP\u2014Centro de F\u00edsica das Universidades do Minho e Porto, Departamento de F\u00edsica da Universidade do Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2317-2759","authenticated-orcid":false,"given":"Jos\u00e9","family":"das Neves","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"CESPU, Instituto de Investiga\u00e7\u00e3o e Forma\u00e7\u00e3o Avan\u00e7ada em Ci\u00eancias e Tecnologias da Sa\u00fade, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2593-1672","authenticated-orcid":false,"given":"Marlene","family":"L\u00facio","sequence":"additional","affiliation":[{"name":"CF-UM-UP\u2014Centro de F\u00edsica das Universidades do Minho e Porto, Departamento de F\u00edsica da Universidade do Minho, 4710-057 Braga, Portugal"},{"name":"CBMA\u2014Centro de Biologia Molecular e Ambiental, Departamento de Biologia, Universidade do Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2018). 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