Influence of Cholesterol Composition on the Association of Serum Mannan-Binding Proteins with Mannosylated Liposomes

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  • Terada Takeshi
    Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Nishikawa Makiya
    Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Yamashita Fumiyoshi
    Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Hashida Mitsuru
    Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University

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説明

In our previous studies, serum mannan-binding protein (MBP) accelerated the uptake by cultured macrophages. The present study was initiated to investigate the kinetics of molecular interaction between mannosylated liposomes and MBP in more details and the effects of lipid composition on the interaction. The analysis was carried out by surface plasmon spectroscopy (SPR) methods, using rabbit serum MBP isolated by affinity chromatography. In SPR studies, neither conventional liposomes nor galactosylated liposomes indicated any interaction, but each mannosylated liposomes had a high response signal corresponding to molecular interaction with immobilized MBP. Association of mannosylated liposomes to serum MBP was not dependent on the lipid composition, suggesting a diffusion-controlled association. Dissociation of the mannosylated liposomes from serum MBP was extremely slow. DSPC/Chol/Man-C4-Chol (90 : 5 : 5, molar ratio) exhibited a slower dissociation rate than DSPC/Chol/Man-C4-Chol (60 : 35 : 5). Clustering of mannose residues on liposomal surfaces might be important in determining the binding affinity of mannosylated liposomes with MBP.

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