Characterization of glucose-mediated insulin release from implantable polymers
Characterization of glucose-mediated insulin release from implantable polymers
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DOI：
10.1021/js9600686
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发表时间：
1996-12-01
影响因子：
3.8
通讯作者：
Langer, R
中科院分区：
文献类型：
--
作者：
Brown, LR;Edelman, ER;Langer, R
我们的特点是葡萄糖敏感，控制释放胰岛素输送系统。当葡萄糖灌注在基质周围的释放介质中时，胰岛素释放速率增加。该系统是由固体，颗粒胰岛素，结合到乙烯-醋酸乙烯酯共聚物（EVAc）矩阵。反馈控制由固定在琼脂糖珠上的葡萄糖氧化酶介导，琼脂糖珠与胰岛素一起沿着掺入EVAc基质中。当溶液中的葡萄糖进入胰岛素递送系统时，产生葡萄糖酸，导致基质的微环境pH值下降。pH值的下降导致胰岛素溶解度的上升，从而导致胰岛素从基质中释放速率的上升。胰岛素浓度增加，在体外和体内响应于葡萄糖输注。增加的胰岛素释放被证明是由一个有限的胰岛素脉冲，需要1小时的最佳恢复期，以实现最大的重复响应的葡萄糖刺激。在4小时内证明了重复脉冲。确定了最佳酶配比。
We characterized a glucose-sensitive, controlled-release insulin delivery system. Insulin release rates increased when glucose was perfused in the release media surrounding the matrix. The system was composed of solid, particulate insulin, incorporated into an ethylene-vinyl acetate copolymer (EVAc) matrix. Feedback control was mediated by the glucose oxidase enzyme immobilized to Sepharose beads, which were incorporated along with insulin into the EVAc matrix. When glucose in solution entered the insulin delivery system, gluconic acid was produced, causing a drop in the microenvironmental pH of the matrix. This fall in pH resulted in a rise in insulin solubility and consequently a rise in the insulin release rate from the matrix. Insulin concentrations increased in vitro and in vivo in response to glucose infusion. The increased insulin release was shown to consist of a finite pulse of insulin that required an optimal recovery period of 1 h to achieve a maximal repeated response to a glucose stimulus. Repeated pulses were demonstrated over a 4 h period. An optimum enzyme ratio was also determined.