Responsive microneedles from phenylborate-functionalized sulfhydryl chitosan for insulin delivery

Diabetes is a chronic disease that seriously threatens human life, health, and safety. Since the advent of insulin, insulin delivery systems have been developed to treat diabetes, or improve the quality of life for diabetic patients, including hydrogels, polymer micelles and microneedles, etc. Herein, a novel functional polymer with multi-level response to glucose, pH, and H₂O₂ was designed and made through sulfhydryl click reaction, in which the modified chitosan was used as cross-linked monomer, (5-methyl-2-(4-(acryloyloxy-methyl phenyl)-1,3,2-dioxabor-5-yl) methyl acrylate (APBEM) as crosslinking agent fabricated in advance, and the 33.2% crosslinking ratio of APBEM and the microstructure of the synthetic polymer were confirmed by relevant physicochemical characterizations. For the multi-level responsiveness of the constructed microneedles (MNs) from the obtained polymer, the sensitive release in 0.5 mM solution of H₂O₂ could be equivalent to the optimal release for the pH sensitivity, signifying a better consuming property of H₂O₂ to lower its side effects, and the insulin release was raised to 66.3% from 12.1% in the same 10 mM solution of glucose by loading of glucose oxidase (GOx), due to the combined action of pH and H₂O₂ dual sensitivity, revealing a remarkable self-regulation release feature. The cytotoxicity assay displayed a suitable biocompatibility of the microneedles, suggesting the gained polymer could become an ideal candidate of responsive delivery system.