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

糖尿病是全世界最重要的卫生保健挑战之一。仅在加拿大，就有两三百万人患有糖尿病，其中80%死于糖尿病并发症，如心脏病。在糖尿病治疗中，通过皮下注射或胰岛素泵给药是最广泛使用的方法。然而，血管和其他糖尿病并发症的持续存在是发病率和死亡率的主要原因，这需要改进胰岛素输送技术，以便根据个体患者的时变血糖水平实时控制胰岛素输送率。目前使用连续葡萄糖传感器与胰岛素泵结合的原型系统还不能提供安全有效的闭环胰岛素输送。建造和维护这样一个输送系统的成本也相当高。除了胰岛素输送，避免严重低血糖导致昏厥、昏迷和死亡，对血糖控制糖尿病的护理也至关重要。严重的低血糖发生在糖尿病中，因为胰岛素对抗（反调节）激素，特别是胰高血糖素的释放有缺陷。本项目将合成葡萄糖反应纳米水凝胶，并将其与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胰岛素递送，以改善血糖控制和自我调节胰高血糖素递送，以避免低血糖选定的患者。通过MEMS结构的设计优化和纳米水凝胶的合成，将证明糖尿病动物（大鼠）血糖控制的改善和低血糖的最小化，这将促使进一步在大型动物和人类身上进行测试。

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.