Development of an injectable supramolecular hydrogel system for prolonged and controlled insulin release in diabetes management.

Insulin injection remains the primary treatment for diabetes. However, patient adherence to this administration method is often poor, and excessive doses can lead to rapid drops in blood glucose, posing a life-threatening risk. This study developed an innovative supramolecular hydrogel system designed for the long-acting and controlled release of recombinant human insulin(rHI). The system comprises methoxy polyethylene glycol-polylactic acid nanoparticles (mPPNPs) and hydrophobically modified dodecyl hydroxypropyl methylcellulose gel (HPMC-C12 Gel), which form a dynamic self-assembled supramolecular network through hydrophobic interactions and multivalent non-covalent bonds. Structural characterization of the materials was conducted using Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC) and background membrane imaging (BMI). The results indicated that the molecular structure of the material was successfully modified, exhibiting shear-thinning rheological properties. In vitro studies revealed that rHI release followed the Korsmeyer-Peppas model, with native polyacrylamide gel electrophoresis (Native-PAGE) and circular dichroism confirming that rHI retained its structural stability even after 7 days of release. In vivo experiments showed that the system effectively reduced blood glucose levels in diabetic mice and maintained stable glucose concentrations for up to 96 h, demonstrating long-lasting hypoglycemic efficacy. Additionally, according to biocompatibility tests, the system exhibited no significant cytotoxicity or injection-related adverse reactions. Overall, this supramolecular hydrogel system presents a novel approach for the precise, controlled release of rHI.