Abstract
Diabetes mellitus, chronic metabolic disease marked by persistent hyperglycemia resulting from inadequate insulin production or impaired action. Despite advancements in glucose-responsive insulin delivery systems, challenges persist such as limited responsiveness to dynamic glucose fluctuations, in vivo biocompatibility, and production scalability with uniform performance. However, insulin-loaded microspheres combined with microfluidics-based technology improve the subcutaneous insulin reservoir and homogeneous microsphere production rate. This study presents a microfluidic-engineered glucose-responsive controlled-insulin release microsphere using Glucose oxidase (GOx) as the glucose-sensing unit and a hybrid carrier composed of poly (lactic-co-glycolic acid) (PLGA) and acid-sensitive acetalated dextran (Ac-dex). The microfluidic-based fabrication method ensured uniform and controllable microsphere size and stable performance with satisfactory batch-to-batch reproducibility. In Streptozotocin (STZ)-induced diabetic mice, the microspheres maintained normal blood glucose levels for at least 20 hours. Absence of additional treatment-induced organ toxicity, systemic inflammation, and low hypoglycemic index ensured that the formulation is safe. Besides, this study provides a promising strategy for closed-loop insulin therapy, with potential clinical applications in improving glycemic control and reducing the burden of diabetes management.