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,
Amphocil and
Abelcet, 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 0.7 mg/kg, respectively) than
Abelcet (ED50 2.7 mg/kg) against L. donovani in a mouse model. Against L. major in vivo,
AmBisome at a dose of 25 mg/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 (ED50 values 0.013 and 0.02 microg/ml, respectively) than
AmBisome and
Abelcet (ED50 values 1.5 and 2.6 microg/ml). This trend was similar in the L. major--PEM model (
Fungizone >
Amphocil >
AmBisome >
Abelcet). THP-1 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.