The Role of Human Serum Proteins in the Uptake of Liposomes and Inhibition of Protein Binding by Polyethylene Glycol (PEG) Coating.

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  • Role of Human Serum Proteins in the Uptake of Liposomes and Inhibition of Protein Binding by Polyethylene Glycol PEG Coating

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We investigated the effects of the lipid composition of liposomes preincubated in human serum and the serum components on the uptake by human macrophage-like U937 cells. Liposomal uptake by U937 cells was affected by its lipid composition; phosphatidylserine facilitated the liposomal uptake and the polyoxyethylene glycol (PEG) coating inhibited. Good correlation was observed between the amount of protein bound to liposomes and the uptake of liposomes by U937 cells. Inactivation of complement and IgG caused the decreases in both association of protein and uptake of liposomes. The percent decrease of uptake comparing with normal human serum was invariable regardless of liposomal lipid compositions. The amount of protein bound to liposomes was quantitated after separation by a spin column method from unbound proteins. The proteins associated with the recovered liposomes were further analyzed by conventional SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Inactivation of complement system or IgG caused a decrease in liposomal uptake by U937 cells and the ratio of the decrease to the uptake in comparison with normal human serum was invariable regardless of liposomal lipid compositions.These results demonstrated that complement systems and immunoglobulins contribute to serum protein mediated liposomal uptake in human.<BR>PEG-coating on liposomal surface resulted in decrease of serum protein bound to liposomes. The sort of proteins associated with the liposomes and effects of inactivation of complement or IgG on the cell uptake were almost same as those of egg yolk phosphatidylcholine (EPC) /cholesterol (CH) liposomes. These results indicate that reticuloendothelial system (RES) -avoiding of PEG-coating liposomes are attributed to the inselective inhibition of serum protein binding probably due to steric barrier effect of PEG chains on the liposome surface, subsequently decrease of affinity with the macrophages.

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  • 膜

    膜 25 (1), 36-44, 2000

    日本膜学会

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