Avaliação do efeito da associação do antimoniato de meglumina e desoxicolato de anfotericina B e da atividade anti-leishmania de uma nova formulação de anfotericina B na infecção experimental com Leishmania (Leishmania) chagasi

Abstract

Despite the discovery of action antileishmanial of Pentavalent antimonials have been the fact that a greater impact on the therapeutic of visceral leishmaniasis, toxic effects and long-term treatment still limit their use. As the second drug of choice is the use of deoxycholate amphotericin B, an antibiotic with high anti-Leishmania activity, and its use is also restricted because of its high toxicity. The major challenge is the development of new drugs, or new formulations of standard drugs, and therapeutic regimens like drugs combinations. Thus, we evaluate the effect of association between meglumine antimoniate and anphotericin B desoxycholate and antileishmanial activity of a new formulation (CAMB) of amphotericin B in the experimental infection with Leishmania (Leishmania) chagasi. Peritoneal macrophages from mice infected with L. chagasi treated with different drugs. Drug activity was determined from the percentage of infected cells in drug-treated cultures in relation to nontreated cultures. In vitro drug interactions were assessed using a modified fixed-ratio method and to classify the interactions, means ΣFICs of 0.5 and 4 were used as cutoffs. The interaction of meglumine antimoniate and DAMB was additive with mean ∑FICs of 0,65 to 1.02 at the IC50 level. To analysis in vitro activity of CAMB was used as control DAMB, and the results showed a similar activity between the two drugs, with IC50 of 0,017 and 0,021µg/mL for CAMB and DAMB respectively, however showed a lower cytotoxicity compared to DAMB. However, in vivo infection mice, CAMB showed no efficacy when administered orally at doses of 1 and 5mg/kg/day for 15 consecutive days, while DAMB injected intraperitoneally was highly effective, suggesting that the use of higher doses and alternative routes of administration of CAMB yet to be evaluated to confirm these findings.