Encapsulation characteristics of nystatin in liposomes: effects of cholesterol and polyethylene glycol derivatives

In this study, we characterized the encapsulation of amphipathic nystatin i nto liposomes with or without cholesterol (CH) and a polyethylene glycol de rivative, distearoyl-N-(monomethoxy poly(ethylene glycol)succinyl)phosphati dylethanolamine (DSPE-PEG). The highest encapsulation efficacy of nystatin into liposomes (151 mu g nystatin/mg lipid) was obtained with a cholesterol -free lipid composition containing 6 mol% of DSPE-PEG. The encapsulation ef ficacy was decreased by the incorporation of CH and improved by the incorpo ration of DSPE-PEG. In liposomes composed of dipalmitoylphosphatidylcholine (DPPC)/CH (2:1, mol/mol), the highest encapsulation efficacy of nystatin l iposomes (84 mu g/mg lipid) was achieved by the addition of DSPE-PEG and hy dration with 9% sucrose solution, as compared with 13 mu g/mg lipid without DSPE-PEG. The encapsulated amount increased with increasing amount of DSPE -PEG used and plateaued at 6 mol% of DSPE-PEG. The optimum molecular weight of PEG in DSPE-PEG was 2000 and a larger molecular weight resulted in lowe r encapsulation. The incorporation of CH affected the self-association of n ystatin with lipid membranes, which was detected by fluorescence measuremen t. The molecular interaction between an amino group in nystatin and a phosp hate group in DSPE-PEG plays an important role in efficient encapsulation o f nystatin. Finally, the encapsulation characteristics of nystatin were com pared with those of amphotericin B (AmB). Nystatin more readily associated with CII-free lipid membranes, but, AmB more readily interacted with DSPE-P EG. The results indicated that the differences in the molecular association of AmB or nystatin with lipids or DSPE-PEG are reflected in the encapsulat ion characteristics in liposomes. (C) 1999 Elsevier Science B.V. All rights reserved.