Molecular localization and state of amphotericin B in PEG liposomes

We investigated the molecular localization and state of amphotericin B:(AmB ) encapsulated in polyethylene glycol (PEG)-coated liposomes. AmB-encapsula ting PEG-liposomes composed of dipalmitoylphosphatidylcholine (DPPC), chole sterol:(CH) and distearoyl-N-(monomethoxy poly(ethylene glycol)succinyl) ph osphatidylethanolamine (DSPE-PEG, average MW of the PEG chain 2000) were pr epared by hydration With 9% sucrose solution and extrusion. The amount of A mB encapsulated in the liposomes increased with incorporation of DSPE-PEG a nd decreased with that of CH. The molecular localization and state of AmB w ere investigated by: PEG/dextran two-phase partition, potassium :permeabili ty measurement, fluorescence quenching measurement and circular dichroism ( CD) spectroscopy. The results suggest that there are two types of AmB local ization in PEG-liposomes, one of which corresponds to the complex of AmB wi th DSPE-PEG on the membrane surface, while the other corresponds to the por e form of AmB in the hydrophobic core of the liposomal membrane. AmB in PEG liposomes was present in both aggregated and monomeric states. (C) 1999 El sevier Science B.V. All rights reserved.