Efeito ansiolítico da nanoemulsão de óleo de girassol contendo fitol em ratas wistar expostas ao labirinto em cruz elevado

Abstract

Phytol, a diterpene with notable effects on the central nervous system, has demonstrated anxiolytic properties in Swiss mice subjected to the elevated plus maze. Despite these findings, limited research has explored the impact of phytol nanoemulsions in animal models of anxiety, particularly in females. The present study aims to evaluate the effects of phytol incorporated into a sunflower oil nanoemulsion on rats exposed to the elevated plus maze. The formulation was developed using the phase inversion method, varying phytol concentration within the oil phase. The most stable formulation, containing the highest diterpene concentration, underwent extensive physicochemical characterization, including droplet size, polydispersity index (PDI), zeta potential, and pH over 35 days. Characterization techniques included fourier transform infrared spectroscopy, transmission electron microscopy, and chromatographic analysis. Additionally, the formulation was tested for hemolytic activity and antioxidant capacity using the DPPH assay and evaluated for its biocompatibility and delivery to the brain using a chicken embryo model. In vivo studies were performed in Wistar rats, with the animals divided into treatment groups (vehicle; diazepam 2 mg/kg; phytol 25 mg/kg; phytol 75 mg/kg; blank nanoemulsion; phytol nanoemulsion 25 mg/kg; and phytol nanoemulsion 75 mg/kg) administered via intraperitoneal injection. The physicochemical analysis revealed that the highest achievable phytol concentration in the nanoemulsion was 2.5%, with an average droplet size of approximately 160 nm, a PDI of 0.235, and a negative zeta potential of -27 mV, showing stability for over 30 days. Behaviorally, a significant reduction in anxiety-like behaviors was observed, as evidenced by increased entries and time spent in the open arms of the maze for rats treated with both the blank and phytol nanoemulsions at varying concentrations, compared to the vehicle group and the free phytol treatment at 25 mg/kg. These findings suggest that the phytol nanoemulsion formulation exhibits superior anxiolytic efficacy compared to the free phytol, highlighting the potential therapeutic advantage of the nanoemulsion system.