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Design, Characterization, and Biopharmaceutical Behavior of Nanoparticles Loaded with an HIV-1 Fusion Inhibitor Peptide.

New therapeutic alternatives to fight against the spread of HIV-1 are based on peptides designed to inhibit the early steps of HIV-1 fusion in target cells. However, drawbacks, such as bioavailability, short half-life, rapid clearance, and poor ability to cross the physiological barriers, make such peptides unattractive for the pharmaceutical industry. Here we developed, optimized, and characterized polymeric nanoparticles (NPs) coated with glycol chitosan to incorporate and release an HIV-1 fusion inhibitor peptide (E1) inside the vaginal mucosa. The NPs were prepared by a modified double emulsion method, and optimization was carried out by a factorial design. In vitro, ex vivo, and in vivo studies were carried out to evaluate the optimized formulation. The results indicate that the physicochemical features of these NPs enable them to incorporate and release HIV fusion inhibitor peptides to the vaginal mucosa before the fusion step takes place.

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