Bile Salt-Induced Disintegration of Egg Phosphatidylcholine Liposomes : A Kinetic Study Based on Turbidity Changes
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概要
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The disintegration kinetics of egg phosphatidylcholine small unilamellar liposomes in various bile salts (nine species) were investigated by monitoring turbidity changes with a stopped-flow apparatus. The pseudo-first-order rate constants obtained as a function of bile salt concentration (up to 25mM) were analyzed based on a two-step model in which a penetration-saturation step of bile salt into the bilayer and a lamellar-micellar transition step were assumed for the disintegration mechanism of the bilayer. The order of the rate of the penetration-saturation step, which is assumed to be a measure of the disintegration ability, was as follows : SCDOC>SDOC>STCDOC>STDOC>STC>SC>SGCDOC>SGDOC>SGC. The results indicated that (1) the dihydroxy bile salts have a greater disintegration ability than the corresponding trihydroxy bile salts, (2) the chenodeoxy bile salts have a greater ability than the corresponding deoxy-bile salts regardless of non-conjugated or conjugated form, (3) the taurine conjugates always have a greater ability than the glycine conjugates. The penetration-saturation rate of the bile salts against the lipid bilayer depends considerably on the chemical nature of each bile salt, varying by a factor of about 10^5. In the conjugated bile salts alone, they were in a narrower range of a factor of 10^3. The physical integrity of liposomes can hardly be maintained in the bile salt-rich intestinal tract but the resulting mixed micelles may contribute substantially to solubilization and enhanced delivery of drugs.
- 公益社団法人日本薬学会の論文
- 1990-05-25
著者
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四ツ柳 智久
愛知学院薬学部製剤学
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池田 憲
名古屋市立大学薬学部
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池田 憲
Faculty Of Pharmaceutical Sciences Nagoya City University
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永田 マリ子
名古屋市立大学・薬
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永田 マリ子
Faculty of Pharmaceutical Sciences, Nagoya City University
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四ッ柳 智久
Faculty of Pharmaceutical Sciences, Nagoya City University
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永田 マリ子
名古屋市立大学病院薬剤部
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四ッ柳 智久
名古屋市立大学・薬
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