To meet women’s need for a safe and effective prevention device against HIV-1, a hydrogel that delivers peptidic anti-retrovirals upon exposure to the HIV-1 carrier was developed. The hydrogel was based on PEG-DBCO and PEG-azide, which were crosslinked using copper free click chemistry. An FDA approved entry inhibitor, Enfuvirtide, was constructed with an additional peptide sequence that undergoes proteolysis by the prostate specific antigen (PSA) present in seminal fluid. This modified Enfuvirtide was also covalently attached to the PEG matrix using copper free click chemistry.
HSSKLQ with kcat/KM of 2.2 M-1s-1 was selected as a suitable linker among the screened PSA substrates for covalent attachment to the hydrogel. The hydrogel displayed a pseudoplastic and thixotropic behavior with an overall viscosity varying between 1516 Pa.s to 2.2 Pa.s, within the biologically relevant shear rates of 0.1 – 100 s-1. It also exhibited viscoelastic properties suitable for vaginal spreading and retention. The gel has highly porous structure verified by SEM which facilitates free movement of PSA and released Enfuvirtide. A hydrogel loaded with 4% of N3-HSSKLQ-Enfuvirtide (HF42) delivered 31.3 ± 8.7% of Enfuvirtide upon exposure to PSA (0.08 mg/ml) at pH 7.4 over 24 hr. This amount is significantly greater than IC50 of Enfuvirtide.
The hydrogel containing Enfuvirtide has been successfully developed to deliver anti-retrovirals upon exposure to PSA in the seminal fluid. The PEG based hydrogel has suitable physiochemical properties for intravaginal application. The hydrogel delivers pharmacologically effective concentrations of peptide anti-retrovirals to prevent women from HIV-1 infection.

PEG-based hydrogel for enzyme responsive delivery of peptide anti-retrovirals

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.