Development and In Vitro/Ex Vivo Characterization of Vaginal Mucoadhesive Bilayer Films Based on Ethylcellulose and Biopolymers for Vaginal Sustained Release of Tenofovir

Abstract

Young women in sub-Saharan Africa have the highest risk of humanimmunodeficiency virus (HIV) acquisition through sexual contact of all groups. Vaginal controlledrelease of antiretrovirals is a priority option for the prevention of sexual transmission of the virus inwomen. In this manuscript, bilayer films were prepared based on ethylcellulose and a naturalpolymer (xanthan or tragacanth gum) plasticized with glycerol and tributylcitrate for tenofovir-controlled release. The mechanical properties and microstructure of the blank films werecharacterized by texture analysis, Fourier transform infrared spectroscopy, and scanning electronmicroscopy. The loaded films were evaluated in simulated vaginal fluid through release and swelling studies and ex vivomucoadhesion assessments. The results show that the preparation method produced bilayer films with adequate mechanicalproperties. The contribution of both layers allowed the sustained release of tenofovir and a mucoadhesion time of up to 360 h. Thetoxicity of the materials was evaluated in three cell lines of vaginal origin. The films constituted by ethylcellulose and xanthan gum ina 2:1 proportion (EX2-D) showed the longest mucoadhesion time, with 15 days of tenofovir-controlled release, zero toxicity, andoptimal mechanical properties. These films are therefore a promising option for offering women a means of self-protection againstthe sexual transmission of HIV.