pH-Responsive Injectable Polyethylene Glycol and Dopamine-Grafted Chitosan Hydrogel for Sustained Insulin Release for Better Diabetic Treatment.

Diabetes is a chronic metabolic disorder caused by insufficient insulin production or resistance, leading to persistent hyperglycemia. Effective glycemic control requires therapies that maintain stable insulin levels and prevent complications. However, conventional insulin injections suffer from poor patient compliance, short therapeutic duration, frequent dosing, and complications such as localized amyloidosis. To overcome these limitations, a pH-responsive injectable dopamine-functionalized methoxy polyethylene glycol-grafted chitosan (mPEG-g-CHT-DA) hydrogel is developed for sustained insulin delivery. The polyethylene glycol (PEG) component enhances hydrophilicity and stability, while dopamine improves bioadhesion and drug-polymer interaction, enabling controlled release. The structural and functional characteristics of the grafted copolymer are confirmed through spectroscopic, thermal, and rheological analyses. Moreover, to investigate better interaction between insulin and polymeric hydrogel network, molecular docking and molecular dynamics have been performed. In vitro studies, including cell viability, biocompatibility, and hemolysis, confirm that chitosan-based graft copolymers and their hydrogels are noncytotoxic, support cell adhesion, and exhibit minimal hemolysis (<5%), demonstrating strong biocompatibility and suitability for blood-contacting biomedical applications. In vivo studies on diabetic mice reveals that the mPEG-g-CHT-DA hydrogel sustains insulin release for 56 h, significantly longer than conventional injections lasting <12 h. In vivo degradation studies reveal that the mPEG-g-CHT-DA hydrogel undergoes rapid biodegradation, leading to nearly complete bioabsorption within 17 days. Histopathological analysis further confirms the hydrogel's biocompatibility and biodegradability, having no observed damage to major organs. These findings demonstrate that the mPEG-g-CHT-DA hydrogel represents a promising drug delivery platform for controlled insulin delivery and long-term glycemic regulation in diabetic therapy.