Vaginal tenofovir disoproxil fumarate - emtricitabine-loaded nanoparticles in films as alternative to oral PrEP
Year: 2017
Type: dissertation
Abstract: The human immunodeficiency virus (HIV) infects millions of people every year. Among those, women account for half of these numbers and heterosexual transmission is the predominant mean of infection. Unfortunately, no cure is available, thus making prevention a cornerstone in the battle against HIV. Oral pre-exposure prophylaxis (PrEP) with daily Truvada® (tenofovir disoproxil fumarate/emtricitabine) has been recently approved in various countries but its efficacy in women is less than optimal, namely due to biological and adherence issues. Thus, alternatives to this preventive modality could be helpful. Topical delivery of the active drugs in Truvada® could be an option but proper selection of delivery platform is required. In this work, nanoparticles-in-film systems are proposed as suitable platforms for the combined vaginal delivery of tenofovir disoproxil fumarate and emtricitabine. Two different approaches were used initially considered for the production of drug-loaded nanoparticles, namely a double emulsion/solvent evaporation method for the production of poly(lactic-co-glycolic acid) (PLGA)-based particles and a spray-drying method for the production of Eudragit® L100- based nanoparticles. Although particles featuring acceptable colloidal properties were obtained, only Eudragit®-based particles (around 687 nm) allowed obtaining suitable association levels of both drugs (2.5% and 5.4% for emtricitabine and tenofovir disoproxil fumarate, respectively). Films based on poly(vinyl alcohol) and pectin were developed and characterized regarding organoleptic, physical-chemical and mechanical properties and considered for particle incorporation. Nanoparticles were physically dispersed in between two sheets of preformed film and the system consolidated by using a hydraulic press. The resulting film presented characteristics considered acceptable for vaginal use and, in particular, featured prolonged drug release for at least 48 h. These results suggest that nanoparticles-in-film may be helpful in achieving a coitus-independent microbicide product that could provide extended protection from HIV transmission. Also, films presented low in vitro cytotoxicity. Overall, proposed nanoparticles-in-film system appears to be suitable for the vaginal delivery of TDF and FTC and may be useful as an alternative to oral PrEP with Truvada® in preventing HIV vaginal transmission.
Author: Mafalda P. Cautela
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2886419191