A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis

The polyene antibiotic, amphotericin B, the gold standard for systemic fungal infections is also a recommended second line treatment for visceral, cutaneous and mucocutaneous leishmaniasis. Acute toxicity has limited the use of amphotericin B but less toxic lipid formulations, AmBisome(R). AmphocilTM and Abelcet(R), have shown potential for the treatment of clinical visceral and mucocutaneous leishmaniasis. This study compares the in vitro and in vivo anti-leishmanial activity of Fungizone and the three lipid formulations. AmBisome and Amphocil were more active (ED50 values 0.3 and 0.7mg/kg, respectively) than Abelcet (ED50 2.7mg/kg) against L. donovani,ani in a mouse model. Against L. major in vivo, AmBisome at a dose of 25mg/kg was the most successful at reducing lesion size, with Amphocil also showing activity while Abelcet was inactive. In the L. donovani - peritoneal macrophage (PEM) model Fungizone and Amphocil were significantly more active (ED,, values 0.013 and 0.02 mu g/ml; respectively) than AmBisome and Abelcet (ED50 values 1.5 and 2.6 mu g/ml). This trend was similar in the L. major - PEM model (Fungizone > Amphocil > AmBisome > Abelcet). THP-I macrophages infected with L. donovani amastigotes showed a different profile with Amphocil = Abelcet > AmBisome > Fungizone. Differences could be due to the interaction of the formulations with the biological milieu and uptake into different cell types. (C) 2000 Elsevier Science B.V, and International Society of Chemotherapy. All rights reserved.