Polypseudorotaxanes of pegylated insulin with cyclodextrins: Application to sustained release system

被引：37

作者：

Higashi, Taishi

Hirayama, Fumitoshi

Arima, Hidetoshi

Uekama, Kaneto

机构：

[1] Sojo Univ, Fac Pharmaceut Sci, Kumamoto 8600082, Japan

[2] Kumamoto Univ, Grad Sch Pharmacuet Sci, Kumamoto 8620973, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 07期

关键词：

cyclodextrin; pegylated insulin; polypseudorotaxane; sustained release system;

D O I：

10.1016/j.bmcl.2007.01.029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The monosubstituted insulin with poly(ethylene glycol) (PEG, MW about 2200) formed polypseudorotaxanes with alpha- and gamma-cyclodextrins (CyDs), by inserting one PEG chain of the pegylated insulin in the alpha-Cyl) cavity and two PEG chains in the gamma-CyD cavity. The pegylated insulin/alpha- and gamma-CyD polypseudorotaxanes were less soluble in water and the release rate of the drug decreased in the order of drug alone > the alpha-CyD polypseudorotaxane > the alpha-CyD polypseudorotaxane. The subcutaneous administration of the pegylated insulin/gamma-CyD polypseudorotaxane in rats significantly sustained plasma glucose levels with an enhanced hypoglycemic effect. The results indicated that the pegylated insulin/CyD polypseudorotaxanes can work as a sustained drug release system and the polypseudorotaxane formation may be useful as a sustained drug delivery technique for pegylated proteins and peptides. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1871 / 1874

页数：4

共 13 条

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