(601c) Glucose-Responsive Supramolecular Hydrogels

Managing blood glucose to control diabetes entails rigorous therapy yet fails to fully restore healthy glycemic control, leading to a myriad number of acute and chronic health complications. Efforts toward more autonomous therapies struggle to match glucose sensing and therapeutic deployment of insulin with temporal fidelity. Beyond this, the delivery of glucagon, which acts to counter the effects of insulin in a bi-hormonal setting or reverse the onset of dangerous and life-threatening low blood glucose events in emergency use, remains a formidable challenge given the limited stability of this protein in formulation. We are engineering hydrogel materials aimed at improving the stability and autonomy of biopharmaceutical agents to improve their short- and long-term efficacy in blood glucose control. Supramolecular materials offer methods to better stabilized these agents in formulation or in concentrated use. Toward autonomous control of activity, crosslinking chemistries based on aryl boronate glucose sensing, along with others actuated through pairing with glucose oxidase enzymes, can furthermore enable the tunable release and bioavailability of insulin and glucagon from hydrogels with rates corresponding to blood glucose-directed therapeutic need. Accordingly, we have developed several suites of hydrogel materials that can sense glucose and adjust their properties to direct the release, bioavailability, and/or potency of insulin and glucagon and evaluated their performance in an assortment of animal models. We furthermore have accessed glucose-fueled dissipative states in multiple platforms of self-assembled materials for rapid response to dangerously low levels of glucose. We envision that these approaches, centered on material-based formulation and delivery of unmodified or minimally modified protein drugs, will yield therapeutic solutions that are responsive, safe, and more efficacious in managing Type-1 diabetes.