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- Title
Structure and toxicity of amphotericin B/triglyceride emulsion formulations.
- Authors
Lance, M. R.; Washington, C.; Davis, S. S.
- Abstract
This paper investigates the relationship between the in-vitro toxicity of amphotericin B/triglyceride emulsion formulations, and their phospholipid composition and method of manufacture. Emulsion toxicity, as measured by the erythrocyte potassium leakage assay, was found to be dependent on the transition temperature of the phospholipid emulsifier, and the thermal history of the emulsion. Emulsions made using unsaturated phospholipids showed a low toxicity irrespective of the method of manufacture. Emulsions made using phospholipids with phase transition temperatures above the maximum process temperature displayed a toxicity comparable to the deoxycholate-solubilized formulation. This toxicity was significantly reduced when such formulations were heated to a temperature above the phase transition temperature for the phospholipid. We interpret these data as demonstrating that the amphotericin molecule must be inserted fully into the phospholipid emulsifier in order to produce a low toxicity emulsion, and that this insertion is critically dependent on the composition of the emulsifier and its phase transition properties.
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 1995, Vol 36, Issue 1, p119
- ISSN
0305-7453
- Publication type
journal article