Cannabidiol-loaded hydrogel contact lenses for on-demand pH regulation and enhanced corneal alkali burn repair.

Corneal alkali burn (CAB) poses a significant therapeutic challenge due to alkali infiltration, bacterial infection, inflammation, and angiogenesis, which collectively hinder recovery. The pH microenvironment after CAB is critical for the healing process, but there are few functional biomaterials for this purpose at present. Herein, we develop a multifunctional hydrogel contact lens (CL) with on-demand release of citric acid (CA) and cannabinoid (CBD), triggered by alkaline conditions, to regulate the microenvironment pH and enhance CAB repair. The CA-functionalized polyvinyl alcohol (PC) and quaternary ammonium chitosan (QCS) are used as hydrogel frameworks, with CBD incorporated as a functional component. The (CBD/QCS/PC, CBD/QPC) hydrogel CL is fabricated using a repeated freeze-thaw process to achieve an interpenetrating network structure. The findings suggest that the 1CBD/QPC hydrogel CL exhibit superior mechanical properties and biocompatibility (hemolysis rate < 0.6 %, cell viability>90 %). These properties enhance wearing comfort and reducing secondary inflammation. Notably, this hydrogel can release CA (52.23 ± 2.78 %) and CBD (59.24 ± 5.15 %) within 24 h under alkaline conditions to neutralize pH, significantly down-regulate the expression level of inflammatory factors and remove hydroxyl radicals. This mechanism fundamentally addressing the secondary damage of residual lye following CAB. Moreover, the hydrogel CL exhibit potent inhibitory effects on the colonization and growth of both E. coli and S. aureus by destroying bacterial membranes, with an inhibition rate > 90 %. In vivo results show that hydrogel CL promote the repair of CAB through anti-inflammatory effects and angiogenesis inhibition. In conclusion, these results demonstrate the potential of this hydrogel CL for treating corneal alkaline burns, providing new insights into treatment of CAB.