ACTIVITY OF A NEW LIPOSOMAL FORMULATION OF AMPHOTERICIN-B AGAINST 2 STRAINS OF LEISHMANIA-INFANTUM IN A MURINE MODEL

The efficacy of a new liposomal formulation of amphotericin B was comp ared to that of amphotericin B deoxycholate (Fungizone) In a murine mo del of visceral leishmaniasis induced by Leishmania infantum. Median e ffective doses (ED50) were determined with two different strains: stra in 1 was obtained from an untreated patient, and strain 2 was obtained from a patient who had received 12.5 g of amphotericin B over 3 years , BALB/c mice were infected intravenously on day 0 with promastigotes and then treated on days 14, 16, and 18 (strain 1) or on days 21, 23, and 25 (strain 2) with the liposomal formulation of amphotericin B (fi ve doses were tested for each strain: 0.05, 0.1, 0.5, 0.8, and 3 mg/kg of body weight) or with conventional amphotericin B (four doses were tested for each strain: 0.05, 0.1, 0.5, and 0.8 mg/kg), Mice in the co ntrol group received normal saline solution, The liposomal amphoterici n B formulation was about three times more active than the conventiona l drug against both strains, ED50 of the liposomal formulation were 0. 054 (strain 1) and 0.194 (strain 2) mg/kg, ED50 of conventional amphot ericin B were 0.171 (strain I) and 0.406 (strain 2) mg/kg, Determinati on of drug tissular levels, 3 days after the last drug administration, showed a drug accumulation in hepatic and splenic tissues much higher after administration of liposomal amphotericin B than after conventio nal amphotericin B. A lack of toxicity was noted in all groups treated with the liposomal formulation.