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Intelligent semi-IPN chitosan-PEG-PAAm hydrogel for closed-loop insulin delivery and kinetic modeling

机译：智能半IPN壳聚糖-PEG-PAAm水凝胶用于闭环胰岛素递送和动力学建模

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摘要

A successful approach to designing an intelligent insulin delivery system could facilitate diabetic patients' lives especially for type 1 diabetes. The aim of the present investigation was to develop an intelligent closed-loop insulin delivery system for implantation. Glucose-responsive semi-IPN hydrogels were synthesized from free radical polymerization of chitosan (CS), acrylamide (AAm) and polyethylene glycol (PEG). Glucose oxidase (GOx) and catalase (CAT) along with insulin were immobilized and loaded into the hydrogels in order to make an intelligent drug carrier, which is able to play the role of an artificial pancreas. The designed glucose responsive hydrogel acts as a self-regulating insulin delivery system and the insulin release rate is associated with the blood glucose level. The loaded hydrogels were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), high performance liquid chromatography (HPLC), and thermal analysis (TGA/DTG). Cell culture tests with fibroblast cells were conducted to perform biocompatibility testing for the drug carrier systems. The effect of the incorporated PEG on the swelling ratio (SR), drug loading capacities (DLC), and entrapment efficiency (EE) of the intelligent semi-IPN hydrogels was investigated using HPLC and UV-vis spectroscopy. Optimization of the hydrogel was also investigated using a full factorial design and by changing the amount of PEG. Kinetic studies were performed using different kinetic models to investigate the insulin release rate.
机译：成功设计智能胰岛素输送系统的方法可以改善糖尿病患者的生活，尤其是1型糖尿病患者。本研究的目的是开发一种用于植入的智能闭环胰岛素输送系统。葡萄糖反应性半IPN水凝胶由壳聚糖（CS），丙烯酰胺（AAm）和聚乙二醇（PEG）的自由基聚合反应合成。葡萄糖氧化酶（GOx）和过氧化氢酶（CAT）与胰岛素一起被固定并装载到水凝胶中，以制备智能药物载体，该药物载体可以起到人造胰腺的作用。设计的葡萄糖反应性水凝胶充当自我调节的胰岛素递送系统，并且胰岛素释放速率与血糖水平相关。使用傅里叶变换红外光谱（FTIR），扫描电子显微镜（SEM），高效液相色谱（HPLC）和热分析（TGA / DTG）对负载的水凝胶进行表征。用成纤维细胞进行细胞培养测试以对药物载体系统进行生物相容性测试。使用HPLC和UV-vis光谱研究了掺入的PEG对智能半IPN水凝胶的溶胀率（SR），载药量（DLC）和包封率（EE）的影响。还使用全因子设计并通过改变PEG的量研究了水凝胶的优化。使用不同的动力学模型进行了动力学研究，以研究胰岛素的释放速率。

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