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-encapsulating PEG-liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (CH) and distearoyl-N-(monomethoxy poly(ethylene glycol)succinyl) phosphatidylethanolamine (DSPE-PEG, average MW of the PEG chain 2000) were prepared by hydration with 9% sucrose solution and extrusion. The amount of AmB encapsulated in the liposomes increased with incorporation of DSPE-PEG and decreased with that of CH. The molecular localization and state of AmB were investigated by PEG/dextran two-phase partition, potassium permeability measurement, fluorescence quenching measurement and circular dichroism (CD) spectroscopy. The results suggest that there are two types of AmB localization in PEG-liposomes, one of which corresponds to the complex of AmB with DSPE-PEG on the membrane surface, while the other corresponds to the pore form of AmB in the hydrophobic core of the liposomal membrane. AmB in PEG liposomes was present in both aggregated and monomeric states.
Moribe
K
K
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.
Maruyama
K
K
Iwatsuru
M
M
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000666:Amphotericin B / Q000032:analysis* / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005453:Fluorescence; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011188:Potassium / Q000493:pharmacokinetics; D012995:Solubility; D013057:Spectrum Analysis
D005079:Excipients; D008081:Liposomes; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; D000666:Amphotericin B; D002784:Cholesterol; D011188:Potassium