A lipid hydrogel to transport and release an anti-HIV-1 peptide into vaginal mucosa

Abstract

The cervicovaginal mucosa is a main portal of entry for the human immunodeficiency virus (HIV). Peptide antiretroviral therapy is a promising treatment to decrease the HIV infection rate, but yet it presents several weaknesses such as poor bioavailability, development of drug resistance and poor ability to reach the mucosal tissue with the effective concentration. In this work, an HIV inhibitor peptide (RE-E1P47) was encapsulated into a lipidic hydrogel (HG) to test its capacity to deliver the peptide to mucosa ex vivo and its pre-exposure prophylactic efficacy to inhibit or limit HIV infection. The proposed HG is made only with lipids and water and has a composition similar to the vaginal fluid that naturally covers the mucosa. Characterization studies with confocal microscopy, ATR-FTIR, SAXS and WAXS reveal that peptide incorporation does not alter the hydrogel's micro- and nanostructure. Permeation and diffusion tests confirm peptide delivery to the surface layers of the mucosal tissue without interaction or diffusion into a vaginal fluid simulant (VFS). Importantly, efficacy studies demonstrate a significant reduction in HIV infection rates of 60% after HG treatment. Thus, we highlight this material formulation as a strong candidate for mucosal topical application, particularly in the development of pre-exposure prophylaxis (PrEP) treatments against HIV-1.