title: Slow-release system of pegylated lysozyme utilizing formation of polypseudorotaxanes with cyclodextrins.
abstract: Poly(ethylene glycol) (PEG, MW 2200) chains were introduced into lysozyme molecule. The resulting pegylated 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Hirayama
authors.forename: Shogo
authors.initials: S
authors.lastname: Yamashita
authors.forename: Shogo
authors.initials: S
authors.lastname: Misumi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
authors.forename: Kaneto
authors.initials: K
authors.lastname: Uekama
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D043862:Rotaxanes / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry; D047391:alpha-Cyclodextrins / Q000737:chemistry; D047408:gamma-Cyclodextrins / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D043862:Rotaxanes; D047391:alpha-Cyclodextrins; D047408:gamma-Cyclodextrins; D014867:Water; D011092:Polyethylene Glycols; C421864:hen egg lysozyme; D009113:Muramidase