Cyclodextrin-Based deep eutectic Solvent-Constructed chitosan eutectogel for therapeutic delivery of Glabridin in diabetic wound management

Diabetic wounds are hard to heal and prone to infection. Glabridin (GLD) can promote wound repair but suffers from poor solubility and photostability. This study developed an adhesive eutectogel (GLD/CS/DES) by combining a deep eutectic solvent (DES) formed from sulfobutyl ether-β-cyclodextrin and levulinic acid with chitosan (CS). The DES not only solubilizes GLD but also acts as a dynamic crosslinker, imparting favorable mechanical properties. The gel enabled sustained GLD release for over 10 days and effectively protected GLD from photodegradation. In vitro antibacterial assays demonstrated > 99% efficacy against S. aureus and E. coli by disrupting bacterial membrane integrity. In an infected diabetic wound model, the gel achieved a wound closure rate of 94.3% by day 21. Mechanistic studies revealed that the gel scavenged reactive oxygen species, inhibited the NF-κB pathway, and promoted macrophage polarization from the pro-inflammatory M1 to the reparative M2 phenotype, thereby ameliorating the immune microenvironment, enhancing angiogenesis, and accelerating tissue regeneration.