Estudo de nanopartículas de antimônio pentavalente e da Hesperidina no tratamento da Leishmaniose Cutânea experimental

Abstract

American Tegumentary Leishmaniasis (ATL) is an infectious-parasitic, non-contagious zoonosis caused by protozoa of the genus Leishmania, which affects the skin and mucous membranes. The therapeutic scheme for ATL in Brazil differs according to the clinical manifestation, species and locality where the infection occurred. Despite the effectiveness of current drugs, they have high toxicity, side effects and parasite resistance. In this sense, several researches are being developed to obtain new pharmaceutical formulations, starting from medicinal inorganic chemistry due to studies with metallic ions presenting promising therapeutic activities, as well as drugs of synthetic origin that represent a significant portion of the pharmaceutical market. The present study aims to synthesize, characterize and evaluate the antileishmania activity of pentavalent antimony nanoparticles (NPSb5+) and the activity of commercial hesperidin (flavanone glycoside) against the species L. (L.) amazonensis, L. (Viannia) guyanensis, L. (V.) braziliensis and L. (V.) naiffi, in vitro and in vivo. In this sense, the NPSb5+ (4 to 0.25 mg/Sb5+/mL) and hesperidin (9 to 0.56 mg/mL) were tested in vitro against promastigotes and amastigotes of Leishmania spp. To ascertain parasite viability and infection rate, respectively; as well as the cytotoxic activity against murine peritoneal macrophages. The in vivo assays were carried out with the species L. (L.) amazonensis, L. (V.) guyanensis and L. (V.) braziliensis in hamsters (Mesocricetus auratus) against two therapeutic protocols. The results demonstrate that the NPSb5+ present promising results in vitro against the Leishmania species tested and did not present cytotoxicity to murine peritoneal macrophages, in the preclinical study they induced the clinical cure of the animals infected with L. (V.) guyanensis (protocol 1 and 2) and L. (V.) braziliensis (protocol 1) and did not show clinical signs indicative of toxicity. Hesperidin showed promising in vitro results against the Leishmania species tested, however, it showed moderate cytotoxicity in murine peritoneal macrophages at the highest concentrations, in the preclinical study hesperidin induced clinical cure in 50% of animals infected with L. (V.) braziliensis treated with GTH2 (Group infected and treated with 4 mg/mL of hesperidin). The continuity of this study is necessary in order to evaluate other parameters, considering the NPSb5+ as strong candidates for the treatment of tegumentary leishmaniasis with greater efficacy than that observed in the treatment with hesperidin.