NMR and ESR study of amphotericin B interactions with various binary phosphatidylcholine/phosphatidylglycerol membranes

Several biologically relevant phospholipids are considered as potential excipients for IV administration liposome's formulation of AMB (Biopharmaceututics Classification System Class IV). On the basis of in vivo bioavaibility studies, DMPC and DMPG were ranked as the first potent encapsulation enhancers for this model drug, especially if one expects to target DMPG rich systems as pulmonary surfactant. Subsequently, dispersions (multilayers) of DMPC, DMPG or in binary systems with various molar ratios were prepared with or without AMB (molar ratios AMB/lipid) and further investigated using the 1H-,31P-NMR methods. It was found that equimolar preparations of DMPG/DMPG exhibited both a good encapsulation of AMB, while also probably able to target pulmonary surfactant. Besides DMPG did not exhibit the same solubilization properties. Conversely, no targeting by DMPC dispersion alone was expected, even if a good solubilization was obtained.

73