Glucose responsive microneedle patch using a reversible and an irreversible crosslinking agents

• Dual-crosslinked PVA hydrogel with BA/CA enhances stability and glucose sensitivity. • Chitosan boosts hydrogel glucose response by 28 %, improving insulin release. • 3D-printed microneedles penetrate skin (465 μm) and withstand 100 N force. • MNP releases 2.75 × more insulin in hyperglycemia vs. glucose-free conditions. • Kinetic modeling confirms glucose-triggered insulin release via anomalous transport. Diabetes mellitus is a prevalent metabolic disorder characterized by elevated blood glucose levels due to insufficient insulin production. Glucose-responsive hydrogels incorporating boric acid (BA) have shown promise for smart insulin delivery through reversible glucose binding. In this study, we developed a polyvinyl alcohol (PVA)-based hydrogel crosslinked with 5 % w/v BA, stabilized with citric acid (CA), and enhanced with chitosan (CS) to improve glucose sensitivity at physiological pH. The optimized hydrogel demonstrated a glucose responsiveness increase from 176.56 % (without CS) to 226.11 % with 10 % w/v CS. This hydrogel was fabricated into a microneedle patch (MNP) for non-invasive insulin delivery. Under hyperglycemic conditions (400 mg/dL glucose), the MNP system achieved a 2.75-fold increase in insulin release compared to glucose-free conditions. Ex vivo insertion tests confirmed effective skin penetration with an average depth of 465 ± 25 µm. These findings highlight the potential of this dual-crosslinked, chitosan-enhanced MNP for smart, glucose-regulated, and patient-friendly insulin delivery in diabetes management.