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 dipalmitoylphosphatidylcholine/ cholesterol (DPPC/CH, 2:1) liposomes after complex formation with distearoyl-N-(monomethoxy poly(ethylene glycol)succinyl) phosphatidylethanolamine (DSPE-PEG). Hydration of lipids was done with 9% sucrose solution.

RESULTS

The encapsulated amount of AmB was 111 microg/mg lipid, which was much higher than that obtained by the same method without DSPE-PEG (14 microg/mg lipid). The amount encapsulated increased with amount of DSPE-PEG used and with PEG molecular weight. Encapsulation efficacy was also influenced by the type of PEG derivatives used and by the modification of AmB, suggesting the involvement of complex formation between AmB and DSPE-PEG. Absorption and 31P-NMR spectral analyses indicated that interactions between the amino and phosphate groups and between the polyene and PEG moieties in AmB and DSPE-PEG, respectively, play an important role in the complex formation.

CONCLUSIONS

Complex formation of AmB with DSPE-PEG allows the highly efficient encapsulation of the drug in liposomes. This simple technique should be applicable to other hydrophobic drugs.