New lipid formulation of amphotericin B: spectral and microscopic analysis.
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.
Laboratoire de Physico-Chimie, Faculté de Pharmacie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Université Paris XI, Faculté de Pharmacie, 5 rue Jean Baptiste Clément, 92296 Châtenay-Malabry Cedex, France.
Malika
M
Larabi
Annette
A
Gulik
Jean-Paul
JP
Dedieu
Philippe
P
Legrand
Gillian
G
Barratt
Monique
M
Cheron
D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000008:administration & dosage*; D008853:Microscopy; D008854:Microscopy, Electron; D010715:Phosphatidylglycerols / Q000008:administration & dosage*
D010715:Phosphatidylglycerols; D000666:Amphotericin B; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine