Injectable nanosized formulation for glucose-responsive insulin delivery

Abstract

Glucose-responsive insulin (GRI) can tremendously facilitate insulin administration via expanding the safe dosage window and reducing injection frequency, as well as enhancing blood glucose control via actively adjusting the insulin release rate. We have previously prepared a robust ion complex-based GRI for type 1 diabetes treatment; however, this complex precipitates easily, which could cause difficulty of injection and inaccuracy of dosage. It remains elusive whether nanoparticulation of this complex could increase suspension stability and retain glucose responsiveness. Herein, we have linked poly (ethylene glycol) (PEG) to 4-carboxy-3-fluorophenylboronic acid (FPBA)-modified poly-ʟ-lysine to obtain PEG-PLL-FPBA. PEG-PLL-FPBA and insulin can form nanosized insulin complex (NIC) with a high insulin loading content and encapsulation efficiency. Of note, the size of the prepared NIC can keep stable for more than 7 days. The NIC showed glucose-stimulated insulin release in vitro with a maximal glucose-responsive index of 400 %. In a streptozotocin (STZ)-induced type 1 diabetic mouse model, the subcutaneously injected NIC could normalize hyperglycemia in 30 min and maintain it normally for 20 h, while minimal toxicity has been identified.