Development and optimization of nanostructured systems loaded with an HIV inhibitory peptide

Human immunodeficiency virus (HIV) constitutes one of the biggest public health problems worldwide. It is estimated that, in 2020, there were 37.7 million people infected with HIV, from which 53% were women. The greater vulnerability of the female gender to HIV makes necessary to develop novel strategies focused specially in the female population. Therefore, development of peptide microbicides together with nanotechnological tools could allow to obtain efficient medications able to cross the vaginal mucosa; which is the main obstacle for drug administration at this level. Biodegradable nanoparticles (NPs) are able to protect active compounds, allow their prolonged release, increase their bioavailability and decrease side effects.

In this study, poly (lactic acid-co-glycolic acid) NPs functionalized with polyethylene glycol (PLGA-PEG) loading an anti-HIV peptide, previously reported by our group, have been designed. In order to provide mucoadhesion and penetration properties through the vaginal mucosa, NPs were coated with chitosan. Anti-HIV peptide was synthesized by Solid Phase Peptide Synthesis (SPPS). NPs were prepared by the modified double emulsion method and they were optimized by means of a design of experiments approach. Moreover, physicochemical properties of the NPs were studied. Optimized NPs showed an average size below 400 nm, a monomodal distribution and highly positive zeta potential (around 30 mV). Furthermore, they were able to encapsulate more than 90 % of the initial peptide.

Optimized NPs possess suitable physicochemical properties for vaginal administration. Subsequently, peptide release and NPs mucoadhesion and penetration in the vaginal mucosa will be further evaluated.