Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
ACS Nano. 2013 May 28;7(5):4194-201. doi: 10.1021/nn400630x. Epub 2013 May 2.
Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial "closed-loop" system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days.
糖尿病是一种葡萄糖调节紊乱的疾病，是一种全球性的负担，影响着全球 3.66 亿人。一种能够模拟胰腺活动并根据血糖水平变化释放胰岛素的人工“闭环”系统有潜力提高患者的依从性和健康水平。在这里，我们开发了一种基于葡萄糖的释放策略，用于使用可注射和酸降解的聚合物网络来自我调节胰岛素的传递。该纳米复合多孔结构是通过带胰岛素的带相反电荷的葡聚糖纳米粒子之间的静电相互作用形成的，并且可以在高血糖状态下通过葡萄糖转化为葡萄糖酸的催化转化而解离并随后释放胰岛素。体外胰岛素释放可以根据葡萄糖浓度呈脉冲式释放。体内研究验证了这些制剂在经皮下给予可降解纳米网络的 1 型糖尿病小鼠中提供了改善的血糖控制。单次注射开发的纳米网络有助于将血糖水平稳定在正常血糖状态（<200mg/dL）长达 10 天。
