Desenvolvimento, caracterização e avaliação da eficácia de sistema auto emulsionável contendo fexinidazol no tratamento da leishmaniose visceral experimental.

Abstract

Leishmaniasis is a group of diseases caused by protozoa of the genus Leishmania. The drugs currently available for treatment are antimonials, amphotericin B, paromomycin and miltefosine, all with limitations. As an alternative to conventional drugs was demonstrated antileishmanicidal activity of a nitroimidazole, with low solubility in water, fexinidazole (FEX). For FEX incorporation, a self-emulsifying drug delivery system (SEDDS) was developed, which is an orally administered system. The objective of this work was to develop a SEDDS containing FEX, to characterize and evaluate the effectiveness of FEX SEDDS for use in the treatment of experimental visceral leishmaniasis. After studying the solubility of FEX in different excipients, a formulation composed of Tween 80®, Span 80®, Kolliphor RH 40® and caprylic caprylic acid triglycerides was developed. FEX SEDDS 10 mg/mL appeared as a clear, yellowish liquid. After dilution in water the nanoemulsion have mean particle size 79 ± 3 nm, polydispersion index (IP) 0.237 ± 0.016, zeta potential -21.9 ± 4.5 and in simulated gastric fluid pH 1.2 (94 ± 9 nm) and simulated intestinal fluid pH 6.8 (97 ± 2 nm), without FEX precipitation in the evaluation in the evaluation by polarized light optical microscopy. The formulation was robust to dilution with mean particle sizes of 81 ± 3 nm, 78 ± 1 nm, 88 ± 4 nm, and 86 ± 3 nm, when diluted 100, 200, 500 and 1000 times in water, respectively. For studies of antileishmania activity, the treatment of mice infected with Leishmania infantum with FEX SEDDS at dose of 50 mg/Kg/day was the only one that led to a significant reduction in the parasitic load (p <0.05) when compared to the white and control SEDDS groups, in the two evaluated organs (spleen and liver) in 10 days. There was no increase in intestinal permeability under the test conditions. These findings suggest that SEDDS FEX may be a promising oral alternative for the treatment of visceral leishmaniasis caused by L. infantum.