ENHANCED ENCAPSULATION OF AMPHOTERICIN-B INTO LIPOSOMES BY COMPLEX-FORMATION WITH POLYETHYLENE-GLYCOL DERIVATIVES

Purpose. A highly efficient method was developed for the encapsulation of amphotericin B (AmB) in liposomes, and the mechanism involved was characterized. Methods. AmB was encapsulated in dipalmitoylphosphatidy lcholine/cholesterol (DPPC/CH, 2:1) liposomes after complex formation with distearoyl-N-(monomethoxy poly(ethylene glycol)succinyl) phosphat idylethanolamine (DSPE-PEG). Hydration of lipids was done with 9% sucr ose solution. Results. The encapsulated amount of AmB was 1 1 1 mu g/m g lipid, which was much higher than that obtained by the same method w ithout DSPE-PEG (14 mu g/mg lipid). The amount encapsulated increased with amount of DSPE-PEG used and with PEG molecular weight. Encapsulat ion efficacy was also influenced by the type of PEG derivatives used a nd by the modification of AmB, suggesting the involvement of complex f ormation between AmB and DSPE-PEG. Absorption and P-31-NMR spectral an alyses indicated that interactions between the amino and phosphate gro ups and between the polyene and PEG moieties in AmB and DSPE-PEG, resp ectively, play an important role in the complex formation. Conclusions . Complex formation of AmB with DSPE-PEG allows the highly efficient e ncapsulation of the drug in liposomes. This simple technique should be applicable to other hydrophobic drugs.