Engineering core-shell polymer microgels to control the onset of glucose-regulated insulin release

Intelligent insulin delivery systems have been a longstanding goal for effective diabetes management with minimized risk of hypoglycemia and reduced discomfort of finger pricks and injections. In this study, core-shell structured microgels are designed to regulate insulin release at physiologically relevant glucose levels. Specifically, a copolymer microgel of poly[(N-isopropylacrylamide)-co-acrylamide-co-(2-acrylamidomethyl-5-fluorophenylboronic acid)] [p(NIPAM-AAm-FPBA)] is prepared as the core to facilitate glucose sensitivity at physiological pH. The neutral hydrophilic poly[oligo(ethylene glycol) methyl ether methacrylate] (pOEGMA) gel shell is added onto the core microgel to enhance the insulin loading capacity and control the glucose-responsive properties of the resultant core-shell microgels. The thickness of the pOEGMA shell directly influences the glucose concentration required to initiate the volume phase transition of the core-shell microgels, allowing for tunable onset (or ‘gate’) of glucose-responsive insulin release. Insulin molecules remain encapsulated within the microgels under hypo- and normoglycemic conditions but are efficiently released in hyperglycemic conditions in response to elevated glucose levels. The pOEGMA-shelled microgels exhibit no cytotoxicity in vitro. Such core-shell microgels highlight their potential as an effective intelligent insulin delivery platform.