title: Polypseudorotaxanes of pegylated insulin with cyclodextrins: application to sustained release system.
abstract: 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-CyD 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 gamma-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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Hirayama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
authors.forename: Kaneto
authors.initials: K
authors.lastname: Uekama
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D015195:Drug Design; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007003:Hypoglycemia / Q000188:drug therapy; D007328:Insulin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D007328:Insulin; D043823:Taxoids; D011092:Polyethylene Glycols; D005947:Glucose