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Antimicrobial Agents and Chemotherapy, December 2003, p. 3774-3779, Vol. 47, No. 12
0066-4804/03/$08.00+0 DOI: 10.1128/AAC.47.12.3774-3779.2003
Copyright © 2003, American
Society for
Microbiology. All Rights Reserved.
Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612,1 Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Université Paris XI, 92296 ChÂtenay Malabry Cedex,3 Centre de Génétique Moléculaire, UPR CNRS 9061, 91198 Gif-sur-Yvette Cedex, France,4 Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, United Kingdom2
Received 7 May 2003/ Returned for modification 20 June 2003/ Accepted 30 August 2003
The aim of the present study was to evaluate the toxicity and the activity of a new lipid complex formulation of amphotericin B (AMB) (LC-AMB; dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, and AMB) that can be produced by a simple process. Like other lipid formulations, this new complex reduced both the hemolytic activity of AMB (the concentration causing 50% hemolysis of human erythrocytes, >100 µg/ml) and its toxicity toward murine peritoneal macrophages (50% inhibitory concentration, >100 µg/ml at 24 h). The in vivo toxicity of the new formulation (50% lethal dose, >200 mg/kg of body weight for CD1 mice) was similar to those of other commercial lipid formulations of AMB. The complex was the most effective formulation against the DD8 strain of Leishmania donovani. It was unable to reverse the resistance of an AMB-resistant L. donovani strain. In vivo LC-AMB was less efficient than AmBisome against L. donovani.
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