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

FEBS Letters

Klibanov, Aleksander L.²  Torchilin, Vladimir P.²  Mori, Atsuhide¹  Huang, Leaf¹ 

[1] Department of Biochemistry, University of Tennessee, Knoxville, TN, USA;Department of Enzyme Engineering, Institute of Experimental Cardiology, Moscow, USSR

关键词: Liposome;    Polyethyleneglycol;    Targeted drug delivery;    Ganglioside GM1;    biotin-cap PE;    biotinamidocaproyl-phosphatidyl ethanolamine;    chol;    cholesterol;    DTPA-SA;    diethylenetriamine pentancetic acid distearylamide complex;    GM1;    monosialoganglioside;    NGPE;    N-glutaryl phosphatidylethanolamine;    PBS;    phosphate-buffered saline;    PC;    egg phosphatidylcholine;    PEG;    polyethyleneglycol;    PEG-PE;    dioleoyl N-(monomethoxy polyethyleneglycol succinyl) phosphatidylethanolamine;    RES;    reticuloendothelial system;   

DOI  :  10.1016/0014-5793(91)80699-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 > PEG2000-PE > 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.

【 授权许可】

Unknown