An insulin delivery system that self-regulates blood glucose levels has the potential to limit hypoglycemic events and improve glycemic control. Glucose-responsive insulin delivery systems have been developed by coupling glucose oxidase with a stimuli-responsive biomaterial. However, the challenge of achieving desirable release kinetics (i.e., insulin release within minutes after glucose elevation and duration of release on the order of weeks) still remains. Here, we develop a glucose-responsive delivery system using encapsulated glucose-responsive, acetalated-dextran nanoparticles in porous alginate microgels. The nanoparticles respond rapidly to changes in glucose concentrations while the microgels provide them with protection and stability, allowing for extended glucose-responsive insulin release. This system reduces blood sugar in a diabetic mouse model at a rate similar to naked insulin and responds to a glucose challenge 3 days after administration similarly to a healthy animal. With 2 doses of microgels containing 60 IU/kg insulin each, we are able to achieve extended glycemic control in diabetic mice for 22 days.

自我调节血糖水平的胰岛素输送系统具有限制低血糖事件和改善血糖控制的潜力。已经通过将葡萄糖氧化酶与刺激响应性生物材料偶联来开发葡萄糖响应性胰岛素递送系统。然而，仍然需要实现理想的释放动力学（即，在葡萄糖升高后数分钟内释放胰岛素，并且释放持续时间为数周）的挑战。在这里，我们开发了在多孔藻酸盐微凝胶中使用封装的葡萄糖响应性，缩醛化葡聚糖纳米粒子的葡萄糖响应性递送系统。纳米颗粒对葡萄糖浓度的变化快速响应，而微凝胶为它们提供保护和稳定性，从而延长了葡萄糖响应性胰岛素的释放。该系统以与裸胰岛素相似的速率降低糖尿病小鼠模型中的血糖，并且在给药后3天对葡萄糖的反应类似于健康动物。使用2剂量的微凝胶，每个微凝胶包含60 IU / kg胰岛素，我们能够在22天的糖尿病小鼠中实现延长的血糖控制。