Effect of cholesterol on the release of amphotericin B from PEG-phospholipid micelles.

Micelles formed from PEG-DSPE solubilize high levels of the poorly water-soluble antifungal amphotericin B (AmB). AmB release from PEG-DSPE micelles is slow in buffer but remarkably rapid in the presence of bovine serum albumin (BSA). Sequential changes in the absorbance spectrum of AmB in PEG-DSPE micelles point to a rapid dissociation of incorporated drug in the presence of BSA. In this context, we have studied micelles formed from PEG-DSPE which coincorporate cholesterol (PEG-DSPE|cholesterol). (1)H NMR measurements point to a lower mobility of lipid in PEG-DSPE|cholesterol micelles compared to PEG-DSPE micelles. The absorbance spectrum of AmB incorporated in PEG-DSPE|cholesterol micelles is distinct from that in PEG-DSPE micelles, which may point to differences in the drug-micelle interaction. AmB release from PEG-DSPE|cholesterol micelles is slow in buffer and in the presence of BSA. The absorption spectrum of AmB in PEG-DSPE|cholesterol micelles remained unchanged in BSA, further supporting stable incorporation and the slow release from the carrier.