Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: studies with poly(ethylene glycol)-coated vesicles.
Well-defined liposome systems have previously established the influence of size, surface charge lipid composition and surface ligands, on in vivo fate and behaviour of model compounds entrapped in liposomes. In the present study, preformed liposomes which quantitatively retain aqueous markers were covalenty coupled via dipalmitoylphosphatidyl-ethanolamine, to the hydrophilic polymer, monomethoxypoly(ethylene glycol) (MPEG 5000). Such liposomes retain the coating in the presence of plasma, and appear to adsorb plasma components more slowly than liposomes without the polymer, shown using an aqueous two-phase partitioning technique. MPEG-coupled liposomes were cleared from the blood circulation up to 30% more slowly than liposomes without MPEG after intravenous administration to mice, despite the unmodified liposomes being of a composition and size shown previously to favour achievement of maximum half-life. It is suggested that the polymer acts as a surface barrier to plasma factors which otherwise bind to liposomes in the blood and accelerate vesicle removal.
Senior
J
J
Academic Department of Medicine, Royal Free Hospital School of Medicine, London, U.K.
Delgado
C
C
Fisher
D
D
Tilcock
C
C
Gregoriadis
G
G
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000097:blood* / Q000737:chemistry; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes; D008657:Metabolic Clearance Rate; D051379:Mice; D010713:Phosphatidylcholines / Q000097:blood* / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000097:blood* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000494:pharmacology*
D001798:Blood Proteins; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D015060:1,2-Dipalmitoylphosphatidylcholine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C010942:1,2-distearoyllecithin