Preexposure prophylaxis (PrEP) using oral or vaginal microbicide is an emerging and effective strategy to prevent HIV transmission. Vaginal film is becoming more acceptable and a convenient dosage form compared to cream, gel and suppository. Extremely poor aqueous solubility of efavirenz (EFV) limits its use as vaginal microbicide. The aim of this study was to develop and evaluate a monomeric surfactant free, rapidly soluble vaginal film of EFV (EZ film). EZ film was prepared using a tetrafunctional block polymer (Tetronic 1107), carrageenan and polyvinyl alcohol (PVA) by solvent evaporation method. First, different solubilizers were screened for EFV solubility, in vitro cytotoxicity and cell membrane integrity assay on HeLa cells. Optimized film was characterized for solid state, mechanical strength, epithelial integrity, in vitro drug release in simulated vaginal fluid (SVF), simulated seminal fluid (SSF) and in vitro anti-HIV activity. Optimized EZ film showed a particle size of 48 ± 3.8 nm with PDI of 0.299. Differential scanning colorimetry (DSC) thermogram suggested the complete amorphization of EFV within the film. EZ film rapidly disintegrated (30 s) with complete release of EFV in SVF and SSF. The film was found to be non-toxic to HeLa cells and showed similar anti-HIV-1 activity as that of EFV in DMSO. EZ film did not show any significant change in the TEER value in HEC 1A cell line. Hence, the findings from the current study strongly suggest that the EZ film could be a cost-effective and convenient dosage form for PrEP of HIV.
Keywords: Efavirenz; HIV; Microbicide; Nanomicelles; Preexposure prophylaxis; Tetronic; Vaginal film.
Copyright © 2020 Elsevier B.V. All rights reserved.