Poly(ethylene glycol)-lipid conjugates inhibit phospholipase C-induced lipid hydrolysis, liposome aggregation and fusion through independent mechanisms.
Poly(ethylene glycol)-phosphatidylethanolamine (PEG-PE) conjugates have been introduced in liposomal compositions. The resulting large unilamellar vesicles were subjected to the action of phospholipase C. Enzyme-promoted vesicle aggregation and fusion were assayed in liposomes containing various proportions of PEG-PE. At PEG-PE concentrations above 1 mol% the rate of phospholipid hydrolysis decreases, perhaps because the PEG moiety hinders the enzyme from reaching the membrane surface. At concentrations above 0.1 mol% vesicle aggregation occurs at a slower rate, presumably because of the repulsive barrier properties or surface-grafted PEG. Lipid mixing decreases in parallel with vesicle aggregation. Finally, liposomal fusion rates measured as mixing of vesicle aqueous contents are decreased at or even below 0.1 mol%. The latter inhibition is due, apart from the reduced rates of lipid hydrolysis, vesicle aggregation and lipid mixing, to a PEG-PE-based stabilization of the lipid bilayer structure. Thus the observed low rates of contents mixing arise from three combined and independent inhibitory effects of PEG-PE.
Basáñez
G
G
Departamento de Bioquímica, Universidad del País Vasco, Bilbao, Spain.
Goñi
F M
FM
Alonso
A
A
D006868:Hydrolysis; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism; D050356:Lipid Metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008561:Membrane Fusion / Q000187:drug effects*; D010714:Phosphatidylethanolamines / Q000378:metabolism / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology*; D013696:Temperature; D010738:Type C Phospholipases / Q000378:metabolism*
D008051:Lipid Bilayers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D011092:Polyethylene Glycols; D010738:Type C Phospholipases