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

Citation
V. Yardley et Sl. Croft, A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis, INT J ANT A, 13(4), 2000, pp. 243-248
Citations number
48
Categorie Soggetti
Microbiology
Journal title
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
ISSN journal
09248579 → ACNP
Volume
13
Issue
4
Year of publication
2000
Pages
243 - 248
Database
ISI
SICI code
0924-8579(2000)13:4<243:ACOTAO>2.0.ZU;2-U
Abstract
The polyene antibiotic, amphotericin B, the gold standard for systemic fung al infections is also a recommended second line treatment for visceral, cut aneous and mucocutaneous leishmaniasis. Acute toxicity has limited the use of amphotericin B but less toxic lipid formulations, AmBisome(R). AmphocilT M and Abelcet(R), have shown potential for the treatment of clinical viscer al and mucocutaneous leishmaniasis. This study compares the in vitro and in vivo anti-leishmanial activity of Fungizone and the three lipid formulatio ns. AmBisome and Amphocil were more active (ED50 values 0.3 and 0.7mg/kg, r espectively) than Abelcet (ED50 2.7mg/kg) against L. donovani,ani in a mous e model. Against L. major in vivo, AmBisome at a dose of 25mg/kg was the mo st 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 value s 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 wit h L. donovani amastigotes showed a different profile with Amphocil = Abelce t > AmBisome > Fungizone. Differences could be due to the interaction of th e formulations with the biological milieu and uptake into different cell ty pes. (C) 2000 Elsevier Science B.V, and International Society of Chemothera py. All rights reserved.