K. Moribe et al., ENHANCED ENCAPSULATION OF AMPHOTERICIN-B INTO LIPOSOMES BY COMPLEX-FORMATION WITH POLYETHYLENE-GLYCOL DERIVATIVES, Pharmaceutical research, 15(11), 1998, pp. 1737-1742
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.