Estudi biofarmacèutic d’un pèptid inhibidor de l’HIV-1 formulat en nanosistemes

Treballs Finals de Grau de Química, Facultat de Química, Universitat de Barcelona, Any: 2017, Tutores: Elisa Vallès Giménez, Ana Cristina Calpena CampmanyWomen in Africa are disproportionately affected by human immunodeficiency virus type 1 (HIV-1) and many are unable or unwilling to negotiate condom use due to cultural/traditional behaviour or simply wants to conceive. For that reason, the development of a drug delivery system loaded with vaginal microbicide would be of greater benefit to inhibit the spread of HIV-1 not only in disadvantaged areas, like Africa, but also at global scale. In this study, different formulations containing a fusion inhibitor peptide as a microbicide have been prepared. These two preparations consist of two nanosystems, poly(lactic-co-glycolid acid (PLGA) coated with polyvinyl alcohol (PVA) nanoparticles (NPs) and 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) large unillamelar vesicles (LUVs), that improve tissue absorption, penetration and targeting for peptide anti-HIV-1 activity. PLGA-PVA NPs were formulated via solvent displacement and POPC LUVs via the hydration of thin film method, both formulations loaded with the peptide. Size, polidispersion index (PdI), zeta potential (Zpot) and entrapment efficiency (EE) were determined to evaluate their properties. It was necessary to evaluate the stability of the liposomes and nanoparticles at 4 ° C by measuring their size and polydispersity over a period of one month and a half. Both formulations were characterized to determine peptide release rate using a synthetic membrane (in vitro study) and vaginal mucosa permeation (ex vivo study). Previously studies had assayed the stability of the peptide using the same condition

Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide

The effective use of fusion inhibitor peptides against cervical and colorectal infections requires the development of sustained release formulations. In this work we comparatively study two different formulations based on polymeric nanoparticles and lipid vesicles to propose a suitable delivery nanosystem for releasing an HIV-1 fusion inhibitor peptide in vaginal mucosa. Polymeric nanoparticles of poly-d,l-lactic-co-glycolic acid (PLGA) and lipid large unilamellar vesicles loaded with the inhibitor peptide were prepared. Both formulations showed average sizes and polydispersity index values corresponding to monodisperse systems appropriate for vaginal permeation. High entrapment efficiency of the inhibitor peptide was achieved in lipid vesicles, which was probably due to the peptide's hydrophobic nature. In addition, both nanocarriers remained stable after two weeks stored at 4 °C. While PLGA nanoparticles (NPs) did not show any delay in peptide release, lipid vesicles demonstrated favorably prolonged release of the peptide. Lipid vesicles were shown to improve the retention of the peptide on ex vivo vaginal tissue in a concentration sufficient to exert its pharmacological effect. Thus, the small size of lipid vesicles, their lipid-based composition as well as their ability to enhance peptide penetration on vaginal tissue led us to consider this formulation as a better nanosystem than polymeric nanoparticles for the sustained delivery of the HIV-1 fusion inhibitor peptide in vaginal tissues