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Establishment of a controlled insulin delivery system using a glucose-responsive double-layered nanogel

机译：使用葡萄糖反应性双层纳米凝胶建立可控的胰岛素递送系统

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Glucose-responsive insulin delivery systems have been proposed as a promising alternative to conventional intramuscular administration methods, which causes low patient compliance due to the requirement of multiple administration. In addition, protein-based glucose-responsive systems using glucose oxidase and lectin have not achieved success in clinical trials because of their low biostability and potential cytotoxicity. In order to overcome these issues, the phenylboronic acid (PBA)-derivatives converted to hydrophilic moieties with an elevated glucose level play a key role in controlled insulin delivery systems due to their better biostability and high biocompatibility. In order to endow glucose-responsiveness to insulin delivery carriers using PBA derivatives, a glycol chitosan (GC)/sodium alginate (SA)-poly(L-glutmate-co-N-3-L-glutamylphenylboronic acid) (PGGA) graft polymer double-layered nanogel is synthesized by N-carboxyanhydride (NCA) polymerization and carbodiimide coupling reactions. The GC/SA-PGGA double-layered nanogel controllably releases insulin at diabetic glucose levels in vitro, and shows high biocompatibility, determined by cell viability and a hemolysis assay. Moreover, controlled insulin release at high glucose levels can be accomplished using the GC/SA-PGGA double-layered nanogel in mouse studies. Therefore, the GC/SA-PGGA double-layered nanogel characterized by glucose-sensitivity and superior biocompatibility may act as a potential platform for advanced insulin delivery systems.
机译：已经提出了葡萄糖反应性胰岛素递送系统作为常规肌肉内给药方法的有前途的替代方法，其由于多次给药的需要而导致低的患者顺应性。另外，使用葡萄糖氧化酶和凝集素的基于蛋白质的葡萄糖反应系统由于其生物稳定性低和潜在的细胞毒性而未能在临床试验中取得成功。为了克服这些问题，由于其更好的生物稳定性和高的生物相容性，转化成具有升高的葡萄糖水平的亲水性部分的苯基硼酸（PBA）-衍生物在受控的胰岛素递送系统中起关键作用。为了使用PBA衍生物赋予葡萄糖对胰岛素递送载体的反应性，乙二醇壳聚糖（GC）/海藻酸钠（SA）-聚（L-谷氨酸-co-N-3-L-谷氨酰苯基硼酸）（PGGA）接枝聚合物通过N-羧基酸酐（NCA）聚合和碳二亚胺偶联反应合成了双层纳米凝胶。 GC / SA-PGGA双层纳米凝胶在体外可控地以糖尿病葡萄糖水平释放胰岛素，并具有高生物相容性，这是通过细胞活力和溶血分析确定的。此外，在小鼠研究中，可使用GC / SA-PGGA双层纳米凝胶实现高葡萄糖水平下胰岛素的受控释放。因此，以葡萄糖敏感性和优异的生物相容性为特征的GC / SA-PGGA双层纳米凝胶可作为先进胰岛素输送系统的潜在平台。

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