Effect of Serum Components from Different Species on Destabilizing Hydrogenated Phosphatidylcholine-Based Liposomes
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概要
- 論文の詳細を見る
It is accepted that some serum components play important roles in enhancing liposome permeability and in facilitating rapid liposome uptake by the mononuclear phagocytic system. In this study we systematically investigated the influence of serum components from different species on complement-mediated immune damage to hydrogenated phosphatidylcholine (HEPC)-based liposomes. Our results demonstrated that when liposomes were incubated with fresh serum from rats or bovines, there was obvious leakage of 5(6)-carboxyfluorescein (CF) from the liposome. However, when liposomes were incubated with fresh serum from humans, rabbits, guinea pigs, mice, and dogs, almost no pronounced leakage from the liposome was observed. These results indicate that the variability of damage to a liposome corresponds to the variability of the animal species from which the serum comes. In addition, leakage of CF from liposomes was completely inhibited by heating at 56℃ for 30 min or by treatment with EDTA. However, such leakage was not blocked by treatment with EGTA/Mg^<2+>, suggesting that the mechanism of lysis of liposomes is due to complement activation via the alternative pathway rather than via the classical pathway. Studies on reconstitution and compatibility further confirm that some serum factors (complement activating factors, CAFs) induce the activation of the complement system, ultimately leading to the lysis of the liposomes. However, CAF from different animal species exhibited corresponding species differences. Meanwhile, under the condition of heating and dialysis experiments, it is obvious that the CAF is susceptible to heat and the dialysed serum sustains biological activity to destabilize liposome following dialysis against a buffer with Ca^<2+> and Mg^<2+>, indicating that the CAF is not a type of low-molecular weight material but a serum protein.
- 公益社団法人日本薬学会の論文
- 1997-08-15
著者
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Kiwada Hiroshi
徳島大学 ヘルスバイオサイエンス研究部薬物動態制御学
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Kiwada Hiroshi
Faculty Of Pharmaceutical Science University Of Tokyo:(present Address)faculty Of Pharmaceutical Sci
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Kiwada Hiroshi
Faculty Of Pharmaceutifal Sciences The University Of Tokushima
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Kamada Haruhiko
医薬基盤研究所 創薬プロテオミクスプロジェクト
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Kamada Haruhiko
Laboratory Of Pharmaceutical Proteomics (lpp) National Institute Of Biomedical Innovation (nibio)
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Kiwada Hiroshi
Department Of Pharmacokinetics And Biopharmaceutics Faculty Of Pharmaceutical Sciences The Universit
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Kamiya Hiroyuki
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Kamada Hitoshi
Institute For Life Support Technology Yamagata Promotional Organization For Industrial Technology
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ISHIDA Tatsuhiro
Faculty of Pharmaceutical Sciences, The University of Tokushima
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LIU Shicheng
Faculty of Pharmaceutical Sciences, The University of Tokushima
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Liu Shicheng
Faculty Of Pharmaceutical Sciences The University Of Tokushima
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Kamada H
Institute For Life Support Technology Yamagata Promotional Organization For Industrial Technology
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Kiwada H
Faculty Of Pharmaceutifal Sciences The University Of Tokushima
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Kiwada Hiroshi
Faculty Of Pharmaceutical Science The University Of Tokushima
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Kiwada Hiroshi
Department Of Pharmacokinetics And Biopharmaceutics Subdivision Of Biopharmaceutical Science Institu
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Ishida Tatsuhiro
Dep. Of Pharmacokinetics And Biopharmaceutics Subdivision Of Biopharmaceutical Sciences Inst. Of Hea
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Ishida Tatsuhiro
Department Of Pharmacokinetics And Biopharmaceutics Subdivision Of Biopharmaceutical Science Institu
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