Anti-inflammatory PEGylated Bilirubin Microneedle Patch for Diabetes Treatment

The long-term hyperglycemic environment could easily cause chronic metabolic inflammation with physiological disorders, exacerbate inflammatory cytokine storms, increase the risk of patients contracting other complications. Thus, to develop glucose-responsive insulin delivery microneedles with anti-inflammatory is of much importance. Herein, a novel in-situ H2O2-sensitive insulin delivery microneedle array patch was constructed for the intelligent management of blood glucose in diabetics, which was integrated with nanoparticles (NPs) to achieve synergistic enhancement of anti-inflammatory and antioxidant functions. Specifically, PEGylated bilirubin (BR) nanoparticles were loaded with insulin and glucose-sensing element glucose oxidase (GOD), named as I@PEG-BR/GOD NPs, which could release drugs in response to high concentrations of glucose. Moreover, bilirubin with potent antioxidant and anti-inflammatory functions could induce reprogramming macrophages to M2 type polarization, which was much beneficial to inhibit inflammation caused by hyperglycemia. In vivo results demonstrated such in situ H2O2-sensitive insulin delivery microneedle array patch had good anti-inflammatory and antioxidant therapeutic efficacy in a mice model of diabetes. This novel glucose-responsive insulin delivery combined with the anti-inflammatory functions of microneedle patches show great promising for the treatment of diabetes with safe controlled release of insulin.