Vakil Ronak, Kwon Glen S
Department of Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin 53705, USA.
Mol Pharm. 2008 Jan-Feb;5(1):98-104. doi: 10.1021/mp700081v. Epub 2007 Dec 27.
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.
由聚乙二醇-二硬脂酰磷脂酰乙醇胺（PEG-DSPE）形成的胶束可溶解高浓度的水溶性差的抗真菌药物两性霉素B（AmB）。在缓冲液中，AmB从PEG-DSPE胶束中的释放缓慢，但在牛血清白蛋白（BSA）存在下则显著加快。PEG-DSPE胶束中AmB吸收光谱的连续变化表明，在BSA存在下，掺入的药物会迅速解离。在此背景下，我们研究了由PEG-DSPE与胆固醇共同形成的胶束（PEG-DSPE|胆固醇）。核磁共振氢谱（¹H NMR）测量结果表明，与PEG-DSPE胶束相比，PEG-DSPE|胆固醇胶束中脂质的流动性较低。掺入PEG-DSPE|胆固醇胶束中的AmB的吸收光谱与PEG-DSPE胶束中的不同，这可能表明药物与胶束之间的相互作用存在差异。在缓冲液和BSA存在下，AmB从PEG-DSPE|胆固醇胶束中的释放都很缓慢。在BSA中，PEG-DSPE|胆固醇胶束中AmB的吸收光谱保持不变，这进一步证明了药物在载体中的稳定掺入和缓慢释放。
