Eficácia in vivo e in vitro de nova formulação lipossomal contendo uma molécula derivada da hederagenina para o tratamento da leishmaniose visceral

Abstract

Leishmaniasis are neglected tropical diseases endemic in 98 countries with an incidence of approximately 2 million new cases per year. Although these diseases were discovered more than 100 years ago, few drugs are currently available for their treatment. In addition, the efficiency of treatment based on existing drugs is limited in terms of its toxicity, the presence of biological resistance and the duration of treatment. Thus, it is necessary and important to continuously search for new treatments for these diseases, especially through the use of less toxic compounds and more efficient delivery systems. The aim of this study was to evaluate the effectiveness of a new liposomal formulation containing a molecule derived from hederagenin (FL-DHe), a pentacyclic triterpenoid obtained from the fruits of Sapindus saponaria, in the treatment of visceral leishmaniasis. The developed formulation showed the production of liposomes with an average of 141 nm, polydispersion index of 0.12 with zeta potential of -19 mV. The effectiveness of the formulation in inhibiting the proliferation of Leishmania infantum amastigotes infecting macrophages, in vitro, was confirmed by presenting selectivity indexes (IS = 8.46) higher than the positive control using Amphotericin B (IS <2). The formulation also showed low toxicity on macrophages, kidney and liver cells. In animal toxicity tests, the groups were treated with different concentrations of FL-DHe and, after biochemical and histopathological analyzes, the non-toxic character was maintained, with no significant differences (p≥ 0.05), when compared to the PBS control group, in none of the concentrations. The results on its activity in an animal model showed that, at the dose used, there were no statistical differences between the group treated with FL-DHe, compared to untreated infected groups. However, an increase in parasitic load in the groups treated with empty liposomes (FL-V) may indicate that the components of the formulation influenced the action of the compound. In summary, the results demonstrated the great leishmanicidal potential of the formulation and its low toxicity in vitro, requiring studies in favor of the refinement of its therapeutic protocol and liposomal formulation, aiming to enhance the activity of the compound in a murine model.