Slow-release system of pegylated lysozyme utilizing formation of polypseudorotaxanes with cyclodextrins
Slow-release system of pegylated lysozyme utilizing formation of polypseudorotaxanes with cyclodextrins
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DOI：
10.1016/j.ijpharm.2009.02.017
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发表时间：
2009-06-05
影响因子：
5.8
通讯作者：
Uekama, Kaneto
中科院分区：
文献类型：
--
作者：
Higashi, Taishi;Hirayama, Fumitoshi;Uekama, Kaneto
将聚乙二醇（PEG，MW 2200）链引入溶菌酶分子中。通过在 α-CyD 腔中插入一条 PEG 链，在 γ-CyD 腔中插入两条 PEG 链，所得聚乙二醇化溶菌酶与 α- 和 γ- 环糊精（分别为 α- 和 γ-CyD）形成聚拟轮烷。聚乙二醇化溶菌酶/CyD聚拟轮烷的水溶性较差，聚乙二醇化蛋白质的释放速率按照聚乙二醇化溶菌酶＞γ-CyD聚拟轮烷＞α-CyD聚拟轮烷的顺序降低。从聚拟轮烷中释放的聚乙二醇化溶菌酶的酶活性与单独的聚乙二醇化蛋白质的酶活性相同，表明活性并未因聚拟轮烷形成而降低。结果表明，聚乙二醇化溶菌酶/CyD聚拟轮烷可以作为缓释系统，与CyDs形成聚拟轮烷可以作为制备聚乙二醇化蛋白质和肽缓释系统的新策略。 (C) 2009 Elsevier B.V. 保留所有权利。
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.