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

Abstract

Lipid hydrogel; Peptide; Vaginal mucosa

Hidrogel lipídico; Péptido; Mucosa vaginal

Hidrogel lipídic; Pèptid; Mucosa vaginal

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.

This work was supported by funds from the Spanish Ministry of Science and Innovation with Ayudas para contratos para la formación de doctores en empresas “Doctorados Industriales”, DIN2019-010777, Bicosome S. L., the Mechanism for the Recovery and Resilience of the European Union and MICINN with the CPP2021-008954 project and PID2021-124848OB-I00 project. This work was also supported by grants from the Spanish Health Institute Carlos III (ISCIII, PI20/00160), cofunded by ERDF/ESF, “A way to make Europe”/“Investing in your future”, from MCIN/AEI/10.13039/501100011033 and the European Union “Next Generation EU”/PRTR (CNS2022-135549 and PID2023-149204OB-I00), the Fundació La Marató TV3 (201814-10 FMTV3) and Gilead fellowships (GLD21/00049 and GLD23/00012) to M. G. M. J. G. and I. H. acknowledge the Grant PID2021-122216-OB-I00 received from the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund.