Influence of the steric barrier activity of amphipathic poly(ethyleneglycol) and ganglioside GM1 on the circulation time of liposomes and on the target binding of immunoliposomes in vivo.
A series of dioleoyl N-(monomethoxy polyethyleneglycol succinyl)phosphatidylethanolamine (PEG-PE) of different polymer chain length was used in this study. Both the activity of PEG-PE in prolonging the circulation time of liposomes and the relative steric barrier activity of amphipathic polymer, measured by a liposome agglutination assay, were found to be directly proportional to the chain length of PEG-PE (PEG5000-PE greater than PEG2000-PE greater than PEG750-PE). However, PEG5000-PE caused a reduced target binding of immunoliposomes in mice due to its overly strong steric barrier activity. The best PEG-PE species supporting the target binding of immunoliposomes was PEG2000-PE, the activity of which was compatible to that of ganglioside GM1. However, GM1 only showed a weak steric barrier activity, suggesting a different mechanism for this glycolipid.
Mori
A
A
Department of Biochemistry, University of Tennessee, Knoxville 37996-0840.
Klibanov
A L
AL
Torchilin
V P
VP
Huang
L
L
D000818:Animals; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins / Q000494:pharmacology; D004337:Drug Carriers; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D009391:Nephelometry and Turbidimetry; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D019809:Streptavidin; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D005677:G(M1) Ganglioside; D011092:Polyethylene Glycols; D019809:Streptavidin