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Journal of Drug Delivery
Volume 2011, Article ID 195146, 9 pages
http://dx.doi.org/10.1155/2011/195146
Research Article

Effects of Selected Anionic β-Cyclodextrins on Persistence of Blood Glucose Lowering by Insulin Glargine after Subcutaneous Injection to Rats

1Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
2Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan
3CyDex Pharmaceuticals, Inc., Lenexa, KS 66214-1643, USA

Received 29 July 2011; Accepted 19 September 2011

Academic Editor: Roberta Cavalli

Copyright © 2011 Keiko Uehata et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.