Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Carbohydr Polym. 2017 May 15;164:42-48. doi: 10.1016/j.carbpol.2017.01.074. Epub 2017 Jan 23.
Sustained and controllable release of insulin is strongly required to achieve the ideal treatment of diabetes. We previously developed "self-assembly PEGylation retaining activity (SPRA) technology" via a host-guest interaction between PEGylated β-cyclodextrin and adamantane-appended insulin, and resulting PEGylated insulin was termed SPRA-insulin. So far, we also demonstrated that covalently PEGylated insulin forms polypseudorotaxanes (PPRXs) with cyclodextrins (PPRX technology). In the present study, we designed and evaluated the combination system of SPRA technology and PPRX technology to achieve a sustained and controllable release system of insulin. SPRA-insulin formed PPRXs with α-cyclodextrin and γ-cyclodextrin. In addition, SPRA-insulin/cyclodextrin PPRXs provided sustained and controllable release of insulin beyond the each single technology both in vitro and in vivo. These results suggest that the combination system of SPRA technology and PPRX technology is useful for design of a sustained and controllable release system of insulin.
胰岛素的持续可控释放对于实现糖尿病的理想治疗至关重要。我们之前通过聚乙二醇化β-环糊精和金刚烷修饰胰岛素之间的主客体相互作用开发了“自组装聚乙二醇化保留活性（SPRA）技术”，并将聚乙二醇化胰岛素命名为 SPRA-胰岛素。到目前为止，我们还证明了共价聚乙二醇化胰岛素与环糊精形成聚轮烷（PPRX）（PPRX 技术）。在本研究中，我们设计并评估了 SPRA 技术和 PPRX 技术的组合系统，以实现胰岛素的持续可控释放系统。SPRA-胰岛素与α-环糊精和γ-环糊精形成 PPRX。此外，SPRA-胰岛素/环糊精 PPRX 提供了胰岛素的持续可控释放，其效果超过了每种单一技术在体外和体内的效果。这些结果表明，SPRA 技术和 PPRX 技术的组合系统可用于设计胰岛素的持续可控释放系统。
