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

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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.