Lipid formulations of amphotericin B in the treatment of experimental visceral leishmaniasis due to Leishmania infantum

Abstract

Despite significant antileishmanial activity of amphotericin B (AmB) in vitro, the use of the deoxycholate formulation (Fungizone®) is limited because of serious side effects. Lipid formulations of AmB have been proposed to reduce this toxicity. We compared the tolerance and efficacy of the conventional AmB prepared with deoxycholate, AmB emulsified in Intralipid® 20%, amphotericin B lipid complex (Abelcet®), and liposomal AmB (AmBisome®) in a murine model of visceral leishmaniasis induced by Leishmania infantum. Control groups included untreated mice and mice treated with the pentavalent antimonial (Glucantime®). Balb/C mice were infected intravenously on day 0 with 10 7 promastigotes of L. infantum, then treated from days 7 to 17 (early treatment group) or from days 60 to 70 (delayed treatment group). Glucantime® was administered daily by intraperitoneal injection, whereas AmB formulations were administered intravenously on alternate days. On days 20, 60 and 120 in the early treatment group and 72 and 125 in the delayed treatment group, parasite burdens were determined in liver, spleen, and lungs by subculturing using a microtitration method. Abelcet® (12 mg/kg) and AmBisome® (12 mg/kg) completely eradicated the parasites from the tissues. Both of these lipid formulations enabled higher dosages to be tolerated, and were remarkably more effective than Fungizone® (0·8 mg/kg) and AmB diluted in Intralipid 20% (1.2 mg/kg) in the treatment of murine visceral leishmaniasis due to L. infantum.