A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis |
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Authors: | Yardley V Croft S L |
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Affiliation: | Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK |
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Abstract: | 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 0.7mg/kg, respectively) than Abelcet (ED50 2.7mg/kg) against L. donovani 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 (ED50 values 0.013 and 0.02 μg/ml, respectively) than AmBisome and Abelcet (ED50 values 1.5 and 2.6 μg/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. |
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Keywords: | Amphotericin B Macrophage Leishmania Lipid formulation |
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