Intelligent microneedle patch based on functionalized alginate and chitosan for long-term self-regulated insulin delivery

Abstract

Severely diabetic patients need insulin input to maintain the body's glycemic balance. However, traditional injection methods are often associated with poor adherence and an increased risk of hypoglycemia. Microneedle technology offers a promising solution by minimizing pain and trauma during insulin administration. Nonetheless, achieving prolonged glycemic control by microneedle with high insulin loading remains a significant challenge. Herein, we introduce an innovative microneedle patch that draws inspiration from the elegant light-induced blooming of water lily petals. The patch features a glucose-responsive hydrogel network crafted from two modified polysaccharide polymers, which enables the delivery of long-acting insulin without depending on glucose oxidase. By incorporating phenylboronic acid-modified sodium alginate, quaternary ammonium chitosan, and polyvinyl alcohol into a hydrogel matrix, we have created a microneedle system that harbors dynamic borate ester linkages and electrostatic attractions, resulting in heightened sensitivity to blood glucose levels. The electrostatic interaction acts as a relatively stable crosslinking point, balancing the dynamic reproducibility response based on the borate ester bond. This self-adaptive hydrogel can regulate insulin-controlled release by responding to changes in glucose concentration. Herein, we achieved massive insulin loading (20 IU) with long lasting glycaemic control (48 h) in a single treatment of diabetic SD rats.