title: Effects of Selected Anionic β-Cyclodextrins on Persistence of Blood Glucose Lowering by Insulin Glargine after Subcutaneous Injection to Rats.
abstract: Insulin glargine is a synthetic long-acting insulin product used for patients with diabetes mellitus. In this study, to obtain the further desirable blood-glucose lowering profile of insulin glargine, we investigated the effects of β-cyclodextrin sulfate (Sul-β-CyD) and sulfobutylether β-cyclodextrin (SBE7-β-CyD) on physicochemical properties of insulin glargine and pharmacokinetics/pharmacodynamics of insulin glargine after subcutaneous injection to rats. Sul-β-CyD and SBE7-β-CyD increased solubility of insulin glargine. SBE7-β-CyD suppressed the formation of oligomer and enhanced the dissolution rate of insulin glargine from its precipitate, compared to that of Sul-β-CyD. Additionally, we revealed that after subcutaneous administration of an insulin glargine solution, SBE7-β-CyD, but not Sul-β-CyD, increased bioavailability and sustained the blood-glucose lowering effect, possibly due to the inhibitory effects of SBE7-β-CyD on the enzymatic degradation at the injection site. These results suggest that SBE7-β-CyD could be a useful excipient for sustained release of insulin glargine.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Uehata
authors.forename: Takayuki
authors.initials: T
authors.lastname: Anno
authors.forename: Kayoko
authors.initials: K
authors.lastname: Hayashida
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Hirayama
authors.forename: Naomi
authors.initials: N
authors.lastname: Ono
authors.forename: James D
authors.initials: JD
authors.lastname: Pipkin
authors.forename: Kaneto
authors.initials: K
authors.lastname: Uekama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima