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基于伴刀豆球蛋白 A-糖亲和性的葡萄糖响应核壳微球的调控基础和推注胰岛素释放。

Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity.

机构信息

State Key Laboratory of Chemical Resource Engineering & Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, PR China.

Complex and Intelligent Systems Research Center, East China University of Science and Technology, Shanghai, PR China.

出版信息

Int J Biol Macromol. 2018 Jul 1;113:889-899. doi: 10.1016/j.ijbiomac.2018.03.030. Epub 2018 Mar 7.

Abstract

Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy. Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements. Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network. Core-shell microspheres were fabricated through a two-step high-speed shear-emulsification method. The morphology was observed by SEM and TEM, and the core-shell structure was confirmed by the differences in chemical composition between core-shell and single-layer microspheres obtained from XPS and IR analysis. In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell. Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material. The released insulin was proved to remain active according to fluorescence and circular dichroism analysis. The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.

摘要

考虑到患者之间胰岛素抵抗的异质性,个体化胰岛素治疗可能比传统治疗带来更多益处。因此,在葡萄糖响应型胰岛素输送系统中,应更加关注进一步调节胰岛素释放以满足个体需求。我们的研究表明,使用光交联壳层来调节葡萄糖响应性 ConA-多糖网络中基础和餐时胰岛素释放的可行性。通过两步高速剪切乳化法制备核壳微球。通过 SEM 和 TEM 观察形态,并通过 XPS 和 IR 分析获得的核壳微球和单层微球之间的化学成分差异来确认核壳结构。体外胰岛素释放试验表明,具有或不具有光照射的核壳微球能够响应不同的葡萄糖浓度保持相应的餐时和基础胰岛素释放,但与没有壳的单层微球相比,其突释释放要低得多。同时,由于壳材料中肉桂酸侧基的光诱导环加成反应,光照后胰岛素的释放速率和释放量进一步降低。根据荧光和圆二色性分析,释放的胰岛素被证明仍然具有活性。HDF 细胞活力评估表明,核壳微球没有体外细胞毒性。

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