Injectable nanosized formulation for glucose-responsive insulin delivery.

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. [Display omitted] An injectable and stable nanosized formulation has been developed for glucose-responsive insulin delivery. • A stably dispersed and injectable nanosized insulin formulation is prepared. • The nanoparticles can keep size stable at around 100 nm for more than 7 days. • The formulation shows glucose-stimulated insulin release in vitro and in vivo. • The formulation can maintain normoglycemia > 20 h with negligible hypoglycemia. [ABSTRACT FROM AUTHOR]