Tissue Distribution of ^<111>In-Labeled Uricase Conjugated with Charged Dextrans and Polyethylene Glycol
スポンサーリンク
概要
- 論文の詳細を見る
Uricase (UC) was conjugated with dextran, cationic diethylaminoethyl-dextran (DEAED), and anionic carboxymethyl-dextran (CMD) giving a molecular weight of 10000 by the periodate oxidation method. Their disposition characteristics were studied after intravenous injection (i.v.) in mice. Disposition of the conjugate with activated polyethylene glycol (PEG_2) with a similar molecular weight was also studied for comparison. Tissue distribution of the ^<111>In-labeled UC in these conjugates was evaluated by a tissue uptake clearance index calculated in terms of clearance. After i.v. injection, ^<111>In-UC was slowly eliminated from the circulation and gradually accumulated in the liver, spleen, and kidney. Conjugation with neutral dextran slightly enhanced the uptake of ^<111>In-UC by the liver and spleen, while PEG_2 conjugation decreased the tissue uptake and resulted in extremely long plasma retention. On the other hand, DEAED and CMD conjugation resulted in significant enhancement and reduction of hepatic uptake, respectively. These results demonstrated that the pharmacokinetic behaviour of UC can be widely controlled by chemical modification with macromolecules having adequate physicochemical properties.
- 公益社団法人日本薬学会の論文
著者
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Hashida Mitsuru
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Hashida M
Departments Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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FUJITA Takuya
Department of Biopharmaceutics, Kyoto Pharmaceutical University
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Sasaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Sezaki Hitoshi
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Sezaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Hashida M
Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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TAKAKURA Yoshinobu
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Fujita Takuya
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Takakura Yoshinobu
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Takakura Yoshinobu
Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University
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YASUDA Yoshihisa
Department of Basic Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyoto University
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Fujita T
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Sasaki H
Nagasaki Univ. School Of Medicine Nagasaki Jpn
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Yasuda Yoshihisa
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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