Amphipathic poly(ethylene glycol) 5000-stabilized dioleoylphosphatidylethanolamine liposomes accumulate in spleen.
Relatively small liposomes (d less than 200 nm) composed of dioleoylphosphatidylethanolamine (DOPE) and cholesterol (Chol) and containing dioleoyl-N-(monomethoxypoly(ethylene glycol)succinyl)phosphatidylethanolamine (PEG-PE), with PEG of M(r) 5000 (PEG5000-PE), accumulate in the spleen (approximately 40% i.v. injected dose), unlike dioleoylphosphatidylcholine (DOPC)/Chol/PEG5000-PE liposomes of similar size, which show prolonged circulation in the blood. Spleen accumulation was dependent on the injection dose, PEG-PE concentration, and the PEG chain length. The DOPE/Chol/PEG5000-PE liposomes are plasma stable and morphologically indistinguishable from DOPC/Chol/PEG5000-PE liposomes. These results reveal the significance of the matrix lipid in determining the circulation time of PEG-PE-containing liposomes, and are relevant to the design of liposomes which avoid or accumulate in the spleen.
Litzinger
D C
DC
Department of Biochemistry, University of Tennessee, Knoxville.
Huang
L
L
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism* / Q000493:pharmacokinetics; D051379:Mice; D008813:Mice, Inbred ICR; D010714:Phosphatidylethanolamines / Q000378:metabolism* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D008081:Liposomes; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; C020888:1,2-dielaidoylphosphatidylethanolamine; D002784:Cholesterol