Dihydromyricetin encapsulated gelatin-dialdehyde-beta-cyclodextrin hydrogels for antibacterial application

Dihydromyricetin (DMY), a natural flavonoid compound, has garnered extensive research interests owing to its high pharmaceutical value with antioxidant, anticancer and antimicrobial properties. However, its intrinsic limitation of low water-solubility and poor stability severely obstructs its biomedical applications. Herein, a dynamic imine cross-linking strategy to assemble DMY/DA-beta-CD/gelatin hydrogel (DDG) is reported, with the aim of enhancing DMY bio-efficacy and achieve a synergistic antibacterial effect. DMY can be wrapped by the amphiphilic dialdehyde-beta-cyclodextrin (DA-beta-CD) to form an inclusion compound (DMY/DA-beta-CD), significantly increasing its water-solubility without compromising its sustainable release. Furthermore, the Schiff base reaction between DA-beta-CD and gelatin drive the formation of DDG hydrogel featuring viscoelastic, self-healing and injectability properties, serving as a DMY delivery platform. DMY and DA-beta-CD synergistically inhibited bacterial proliferation, enabling a broad-spectrum antibacterial effect against Escherichia coli and Staphylococcus aureus with over 90% inhibition and good biocompatibility. Our work provides a paradigm for self-assembling DMY inclusion compound into a hydrogel to improve the bio-efficacy of DMY, so that the hydrogel can be used as a carrier for hydrophobic drug delivery with promising applications in the biomedical field.