Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes

Incorporation of dioleoyl N‐(monomethoxy polyethyleneglycol succinyl)phosphotidylethanolamine (PEG‐PE) into large unilamellar liposomes composed of egg posphatidylcholine:cholesterol (1:1) does not significantly increase the content leakage when the liposomes are exposed to 90% human serum at 37°C, yet the liposomes show a significant increase in the blood circulation half‐life (t = 5 h) as compared to those without PEG‐PE(t <30 min). The PEG‐PE's activity to prolong the circulation time of liposomes is greater than that of the ganglioside GM1, awell‐described glycolipid with this activity. Another amphipathic PEG derivative, PEG stearate, also prolongs the liposome circulation time, although its activity is less than that ofGM1. Amphipathic PEGs may be useful for the sustained release and the targeted drug delivery by liposomes.

[1]  H M Patel,et al.  Serum opsonins and phagocytosis of saturated and unsaturated phospholipid liposomes. , 1989, Biochimica et biophysica acta.

[2]  T M Allen,et al.  Large unilamellar liposomes with low uptake into the reticuloendothelial system , 1987, FEBS letters.

[3]  J. Young,et al.  Relationship of effective molecular size to systemic clearance in rats of recombinant interleukin-2 chemically modified with water-soluble polymers. , 1988, The Journal of biological chemistry.

[4]  S. Moghimi,et al.  Tissue specific opsonins for phagocytic cells and their different affinity for cholesterol‐rich liposomes , 1988, FEBS letters.

[5]  A. Gabizon,et al.  Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[6]  L. Huang,et al.  Highly efficient immunoliposomes prepared with a method which is compatible with various lipid compositions. , 1989, Biochemical and biophysical research communications.

[7]  M. Kates.  Techniques of Lipidology , 1972 .

[8]  T. Allen,et al.  Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues. , 1989, Biochimica et biophysica acta.

[9]  L. Huang,et al.  Small, but not large, unilamellar liposomes composed of dioleoylphosphatidylethanolamine and oleic acid can be stabilized by human plasma. , 1989, Biochemistry.

[10]  G. Gregoriadis.  Liposomes as drug carriers : recent trends and progress , 1988 .

[11]  K. Hubner,et al.  Gadolinium-labeled liposomes: targeted MR contrast agents for the liver and spleen. , 1987, Radiology.

[12]  R. Müller,et al.  The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with a block copolymer--poloxamine 908. , 1987, Life sciences.

[13]  S. Pizzo,et al.  A new procedure for the synthesis of polyethylene glycol-protein adducts; effects on function, receptor recognition, and clearance of superoxide dismutase, lactoferrin, and alpha 2-macroglobulin. , 1983, Analytical biochemistry.

[14]  S. Davis,et al.  The organ uptake of intravenously administered colloidal particles can be altered using a non‐ionic surfactant (Poloxamer 338) , 1984, FEBS letters.