Desenvolvimento de nanocápsulas poliméricas contendo extrato de Cannabis sativa com potencial atividade antileishmania

Abstract

Leishmaniasis is a zoonotic and endemic infection in Brazil. Leishmania infantum is the cause of the most severe form of leishmaniasis. Cannabis sativa is a widely used plant, with numerous pharmacological targets with promising application in the treatment of leishmaniasis. Thus, nanotechnology emerges as an innovative area that seeks to cure diseases in a less invasive way and among the existing nanosystems, the polymeric nanocapsule stands out. This nanosystem demonstrates a controlled release of the drug, reducing adverse effects, increasing bioavailability and efficacy. In this perspective, the objective of this study was to develop polymeric nanocapsules containing crude extract of Cannabis sativa flowers for application in promastigote forms of Leishmania infantum. Therefore, the extract was characterized by gas chromatography coupled to mass spectrometry (GC-MS). From this, PCL 80 nanocapsules with the extract were developed through nanoprecipitation, optimized by the Box-Behnken experimental design and functionalized with chitosan and L-PEG 5000. This system was characterized through particle size, polydispersity index (PDI), zeta potential, infrared spectroscopy, scanning electron microscopy, dosing and the encapsulation efficiency analyzed by High Performance Liquid Chromatography (HPLC) and subjected to stability testing, being stored at different temperatures. The viability test in the promastigote form of Leishmania infantum was performed to analyze the IC50 of the nanocapsules. According to GC-MS, the major compound of the extract was cannabidiol. The PCL and extract nanocapsules (NCBDP), extract-containing nanocapsules functionalized with L-PEG (NCBDLP) and chitosan (NCBDQ), presented particle sizes 174.4±1.2, 197±2.6 and 269.8±4.5nm, PDI 0.11±0.02, 0.1±0.04, 0.26±0.02, and zeta potential -32.77±0.9, -24.95±0.5 and +43.31±0.3mV, respectively. Infrared spectroscopy detected the presence of the main functional groups. The nanocapsules presented homogeneity and stability. NCBDP, NCDLP and NCBDQ presented encapsulation efficiency of 99.3%, 99.8% and 99.8%, respectively. The viability test in the promastigote form of Leishmania infantum demonstrated IC50 of 35.04 and 12.50μg/mL, for NCBDP and NCBDQ, respectively. Thus, nanocapsules encapsulated with Cannabis sativa extract represents an alternative for the treatment of visceral leishmaniasis.