Glucose-Responsive Nanosystem Mimicking the Physiological Insulin Secretion via an Enzyme–Polymer Layer-by-Layer Coating Strategy

Abstract

Insulin administration mimicking physiological insulin secretion behavior remains a challenge for the treatment of patients with type I diabetes. Herein, we report a novel glucose-responsive insulin-release nanosystem through an enzyme-polymer layer-by-layer coating strategy on silica vesicles loaded with insulin. With a choice of polyethylenimine with prioritized proton binding capability and glucose specific enzymes in the coating layer, the insulin-release threshold can be adjusted in a desired glucose concentration range 5-20 mM for the first time. In vitro tests show that the insulin release is switched "ON" in response to hyperglycemia (10, 20 mM) and "OFF" to normal glucose level (5 mM) repeatedly. Moreover, in vivo experiments in type I diabetes mice demonstrate that our nanosystem enables a fast glucose response insulin release and regulates the glycemia levels in a normal range up to 84 h with a single administration. In addition, when applied to healthy mice, the nanosystem maintains the blood glucose concentration in the normal range without causing hypoglycemia. Our nanosystem which mimics the physiological insulin secretion has the potential to be developed as a convenient and safe insulin delivery carrier for diabetes treatment.