MEMS-based closed-loop drug delivery devices integrating stimulus-responsive nano hydrogels: Design, fabrication, and testing

糖尿病是全球最重要的卫生保健挑战之一。仅在加拿大，就有2300万人患有糖尿病，其中80%死于糖尿病并发症，如心脏病。对于糖尿病，通过皮下注射或胰岛素泵施用胰岛素是最广泛使用的方法。血管和其它糖尿病并发症作为发病率和死亡率的主要原因的持续存在要求改进胰岛素输送技术，其允许基于时间在真实的时间内控制胰岛素输送速率。目前现有的采用连续葡萄糖传感器与胰岛素泵组合的原型系统尚不能提供安全有效的封闭式血糖监测。回路胰岛素输送。建造和维护这样一个运载系统的费用也相当高。除了胰岛素输注，避免可导致昏厥、昏迷和死亡的严重低血糖对糖尿病护理中的血糖控制也至关重要。糖尿病患者会因胰岛素抵抗（反调节）激素，特别是胰高血糖素的释放缺陷而发生严重的低血糖。在本项目中，葡萄糖响应纳米水凝胶将被合成并与MEMS（微机电系统）结构集成，形成新型闭环胰岛素和胰高血糖素输送装置。这些紧凑的微型装置将提供自我调节的胰岛素输送，以改善葡萄糖控制和自我调节的胰高血糖素输送，以避免选定患者的低血糖症。通过MEMS结构的设计优化和纳米水凝胶合成，将证明糖尿病动物（大鼠）的葡萄糖控制和低血糖最小化的改善，这将促进在大型动物和人类中的进一步测试。

Diabetes is among the most important health care challenges worldwide. In Canada alone, two-three millionpeople have diabetes, of which 80% die as a result of diabetic complications such as heart disease. For diabetescare, insulin administration through subcutaneous injection or insulin pumps is the most widely used method.However, the persistence of vascular and other diabetic complications as the main cause of morbidity andmortality calls for the improvement of insulin delivery technologies that allow for controlling insulin deliveryrates in real time based on time-varying glucose levels of individual patients.Currently existing prototype systems that employ continuous glucose sensors in combination with insulinpumps are not yet capable of providing safe and effective closed-loop insulin delivery. The cost of constructingand maintaining such a delivery system is also rather high. Besides insulin delivery, the avoidance of severehypoglycemia that can lead to fainting, coma, and death, is also critically important to glucose control indiabetes care. Severe hypoglycaemia occurs in diabetes because of defective release of insulin-counteracting(counterregulatory) hormones, particularly glucagon.In this project, glucose-responsive nano-hydrogels will be synthesized and integrated with MEMS(microelectromechanical systems) structures to form new types of closed-loop insulin and glucagon deliverydevices. These compact micro devices will provide self-regulated insulin delivery to improve glucose controland self-regulated glucagon delivery to avoid hypoglycemia in selected patients. Through design optimizationof MEMS structures and nano-hydrogel synthesis, improvement of glucose control and minimization ofhypoglycaemia in diabetic animals (rats) will be demonstrated, which will prompt further testing in largeanimals and perhaps in humans.