Desenvolvimento e atividade antifúngica de nanopartículas de PLGA carregadas com o peptídeo crotalicidina [15-34]

Abstract

Human fungal infections, in the form of topical infections or as systemic infections, have become a significant cause of morbidity. In addition, the antifungal agents normally used to treat these infections have shown limited therapeutic results due to toxic side effects, low efficacy and the emergence of resistant pathogens, making the development of new antifungal agents in the pharmaceutical area of great interest. In this sense, the present study aimed to develop an optimized formulation of PLGA (poly (lactic acid-co-glycolic acid)) nanoparticles to load the Ctn[15-34] peptide, a promising antifungal agent derived from a cathelicidin of the venom gland of the snake Crotalus durissus terrificus. The nanoparticles were synthesized by the double emulsion/solvent evaporation method and had their physicochemical characteristics, stability, release and antifungal activity evaluated. The obtained nanosystem presented homogeneous particles, with a mean size of 213.2 ± 2.00 nm, polydispersity index of 0.044 ± 0.04 and zeta potential of -16.03 ± 1.20 mV, with perfect stability of these parameters by 30 days at 4 °C. An excellent entrapment efficiency was obtained, around 93.3 ± 0.10% and the release profile showed a rapid initial release of the peptide, approximately 27% in the first 24 hours, followed by sustained release for at least 16 days. Another relevant aspect is that the nanoparticles potentiated the antifungal activity of the peptide when compared to its free form, in equivalent concentration, representing a thriving therapeutic approach for the delivery of Ctn[15-34].