Polypseudorotaxanes of pegylated insulin with cyclodextrins: Application to sustained release system
- 作者：Taishi Higashi ; Fumitoshi Hirayama ; Hidetoshi Arima ; Kaneto Uekama
- 关键词：Cyclodextrin ; Pegylated insulin ; Polypseudorotaxane ; Sustained release system
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：1 April 2007
- 卷：17
- 期：7
- 页码：1871-1874
- 文件大小：276 K
摘要
The monosubstituted insulin with poly(ethylene glycol) (PEG, MW about 2200) formed polypseudorotaxanes with α- and γ-cyclodextrins (CyDs), by inserting one PEG chain of the pegylated insulin in the α-CyD cavity and two PEG chains in the γ-CyD cavity. The pegylated insulin/α- and γ-CyD polypseudorotaxanes were less soluble in water and the release rate of the drug decreased in the order of drug alone > the γ-CyD polypseudorotaxane > the α-CyD polypseudorotaxane. The subcutaneous administration of the pegylated insulin/γ-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.