Slow-release system of pegylated lysozyme utilizing formation of polypseudorotaxanes with cyclodextrins

被引:39
作者
Higashi, Taishi [2 ]
Hirayama, Fumitoshi [1 ]
Yamashita, Shogo [2 ]
Misumi, Shogo [2 ]
Arima, Hidetoshi [2 ]
Uekama, Kaneto [1 ]
机构
[1] Sojo Univ, Fac Pharmaceut Sci, Kumamoto 8600082, Japan
[2] Kumamoto Univ, Grad Sch Pharmaceut Sci, Kumamoto 8620973, Japan
关键词
Lysozyme; Pegylated lysozyme; Cyclodextrin; Polypseudorotaxane; Slow-release system; GAMMA-CYCLODEXTRIN; ALPHA-CYCLODEXTRIN; INCLUSION COMPLEXES; DRUG-DELIVERY; GENE DELIVERY; LINEAR POLYETHYLENIMINE; POLY(ETHYLENE GLYCOL); ORGANIC COMPOUNDS; STARCHY MATERIALS; X-RAY;
D O I
10.1016/j.ijpharm.2009.02.017
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Poly(ethylene glycol) (PEG, MW 2200) chains were introduced into lysozyme molecule. The resulting pegylayed lysozyme formed polypseudorotaxanes with alpha- and gamma-cyclodextrins (alpha- and gamma-CyDs, respectively), by inserting one PEG chain in the alpha-CyD cavity and two PEG chains in the gamma-CyD cavity. The pegylated lysozyme/CyD polypseudorotaxanes were less soluble in water and the release rate of the pegylated protein decreased in the order of the pegylated lysozyme > the gamma-CyD polypseudorotaxane > the alpha-CyD polypseudorotaxane. The enzymatic activity of the pegylated lysozyme released from the polypseudorotaxanes was the same as that of the pegylated protein alone, indicating no decrease in the activity through the polypseudorotaxane formation. The results indicate that the pegylated lysozyme/CyD polypseudorotaxanes can work as a slow-release system, and the polypseudorotaxane formation with CyDs may serve as a new strategy for the preparation of slow-release system of pegylated proteins and peptides. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:26 / 32
页数:7
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