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. 2004 Aug 30;1664(2):172-81.
doi: 10.1016/j.bbamem.2004.05.003.

New lipid formulation of amphotericin B: spectral and microscopic analysis

Malika Larabi  1 , Annette Gulik, Jean-Paul Dedieu, Philippe Legrand, Gillian Barratt, Monique Cheron
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Free article

New lipid formulation of amphotericin B: spectral and microscopic analysis

Malika Larabi et al. Biochim Biophys Acta. .
Free article

Abstract

UV-visible and dichroic spectrum analysis and electron microscopy have been used to characterize a new amphotericin B (AmB) lipid formulation prepared by a solvent displacement process. The composition was dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) in molar ratio DMPC/DMPG/AmB 7:3:5, a similar composition to that of Abelcet. Although the latter has a "ribbon-like" structure, our process gave a thin disc-like structure. Analysis of circular dichroism (CD) and UV-visible spectra of formulations containing different percentages of AmB revealed that a minimum of AmB self-association was observed with 7:3:5 molar ratio. Varying the lipid ratio (DMPC/DMPG) while maintaining the fixed ratio of AmB yielded similar results when DMPC was in excess (DMPC/DMPG from 10:0 to 6:4). However, when the ratio was between 5:5 to 3:7, AmB self-aggregation increased. For compositions rich in DMPG (2:8 and 0:10), inversion of the CD spectrum was observed. The influence of the lipid composition on the morphology of the complex was also evident in electron microscopy. DMPC/DMPG/AmB (10:0:5) gave large unfracturable lamellae. The presence of DMPG shortened the lamellae, which often appeared as disc-like structures. AmB content, the presence of DMPG and the preparation process all contribute to generating these original structures with particular CD spectra.

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