In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.
The activities of four amphotericin B formulations, Fungizone, AmBisome, Amphocil, and Abelcet, were compared in vitro and in vivo against Trypanosoma cruzi infections. In vitro, Fungizone and Amphocil were highly active against T. cruzi Y strain amastigotes in macrophages with 50% effective dose (ED50) values of 0.027-0.028 microg/ml, which were 7-fold and 42-fold more active than AmBisome and Abelcet, respectively. In vitro activities of all formulations against T. cruzi amastigotes in Vero cells were similar, with ED50 values in the range of 2.0-4.2 microg/ml. Acute infections of the T. cruzi Y strain in BALB/c mice were suppressed in all animals by a single 25 mg/kg dose of the liposomal formulation AmBisome. At the same dose, the two other lipid formulations, Amphocil and Abelcet, increased the survival rate but did not suppress infection in all animals.
Yardley
V
V
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Croft
S L
SL
D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014355:Chagas Disease / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D007275:Injections, Intravenous; D008055:Lipids; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000302:isolation & purification; D014709:Vero Cells / Q000187:drug effects
D000981:Antiprotozoal Agents; D004337:Drug Carriers; D008055:Lipids; D000666:Amphotericin B