Development and In Vitro/Ex Vivo Characterization of Vaginal Mucoadhesive Bilayer Films Based on Ethylcellulose and Biopolymers for Vaginal Sustained Release of Tenofovir
- 8 April 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Biomacromolecules
- Vol. 21 (6), 2309-2319
- https://doi.org/10.1021/acs.biomac.0c00249
Abstract
Young women in sub-Saharan Africa have the highest risk of HIV acquisition through sexual contact of all groups. Vaginal controlled release of antiretrovirals is a priority option for the prevention of sexual transmission of the virus in women. In this manuscript, bilayer films were prepared based on ethylcellulose and a natural polymer (xanthan or tragacanth gum) plasticized with glycerol and tributylcitrate for Tenofovir controlled release. The mechanical properties and microstructure of the blank films were characterized by texture analysis, FTIR and SEM. The loaded films were evaluated in simulated vaginal fluid through release and swelling studies and ex vivo mucoadhesion assessments. The results show that the preparation method produced bilayer films with adequate mechanical properties. The contribution of both layers allowed the sustained release of Tenofovir, and a mucoadhesion time of up to 360h. The toxicity of the materials was evaluated in three cell lines of vaginal origin. The films constituted by ethylcellulose and xanthan gum in a 2:1 proportion (EX2-D) showed the longest mucoadhesion time, with 15 days of Tenofovir controlled release, zero toxicity and optimal mechanical properties. These films are therefore a promising option for offering women a means of self-protection against the sexual transmission of HIV.Keywords
Funding Information
- Ministry of Science, Innovation and Universities
- European Commission (MAT2016-76416-R)
- Agencia Estatal de Investigaci??n (MAT2016-76416-R)
This publication has 51 references indexed in Scilit:
- Freeze-dried bioadhesive vaginal bigels for controlled release of TenofovirEuropean Journal of Pharmaceutical Sciences, 2018
- FAME‐04: A Phase 1 trial to assess the safety, acceptability, pharmacokinetics and pharmacodynamics of film and gel formulations of tenofovirJournal of the International AIDS Society, 2018
- Influence of Chitosan Swelling Behaviour on Controlled Release of Tenofovir from Mucoadhesive Vaginal Systems for Prevention of Sexual Transmission of HIVMarine Drugs, 2017
- Differential Mechanisms of Tenofovir and Tenofovir Disoproxil Fumarate Cellular Transport and Implications for Topical Preexposure ProphylaxisAntimicrobial Agents and Chemotherapy, 2016
- Biodegradable Film for the Targeted Delivery of siRNA-Loaded Nanoparticles to Vaginal Immune CellsMolecular Pharmaceutics, 2015
- Development and characterization of a solid dispersion film for the vaginal application of the anti-HIV microbicide UAMC01398International Journal of Pharmaceutics, 2014
- Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infectionJournal of Antimicrobial Chemotherapy, 2014
- Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 InfectionClinical Medicine Insights: Women's Health, 2014
- MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other CompartmentsPLOS ONE, 2013
- Overview of microbicides for the prevention of human immunodeficiency virusBest Practice & Research Clinical Obstetrics & Gynaecology, 2012