부산대학교 도서관

The main drawbacks with current antiretroviral therapies are the occurrence of multi-drug resistance viruses and the reduced capacity of these drugs to access tissues. Hence, new therapeutic alternatives to fight the spread of HIV are based on peptides that inhibit the early steps of HIV-1 fusion in target cells, which avoids side effects such as therapy resistance. Unfortunately, the molecules used have weaknesses such as poor bioavailability; a short half-life; fast removal; and little capacity to cross physiological barriers such as vaginal fluid, which protects the vaginal epithelium from any foreign agents reaching it, especially biomolecules such as peptides. For these reasons, the main objective of this research was to develop, optimized and characterize polymeric Nanoparticles (NPs) covered with glycol chitosan (GC) to introduce and release peptides derived from GB virus C that inhibit HIV-1 into the vaginal mucosa. In vitro release and ex vivo studies were carried out using pig vaginal mucosa and the peptides were determined by an HPLC MS/MS-validated method. Moreover, the peptides were labeled with 5(6)-carboxyfluorescein and entrapped within the NPs to carry out in vivo studies and to evaluate the penetration and toxicity of the NPs in the pig vaginal mucosa. The results suggest that the fusion inhibitor peptides developed and loaded into the NPs coated with GC might be a new way to fight HIV-1, as the formulation could reach the human epithelial mucosa and release the peptide without any side effects.