A novel antioxidant and anti-inflammatory carboxymethylcellulose/chitosan hydrogel loaded with cannabidiol promotes the healing of radiation-combined wound skin injury in the 60Co γ-irradiated mice.

BACKGROUND

Combined radiation and wound skin injury (RW) are frequently observed in patients undergoing tumor surgery plus radiotherapy, and but specific treatment is lacking. Chitosan (CS) and carboxymethyl cellulose (CMC) are commonly used to prepare hydrogel with good biocompatibility and low toxicity. Cannabidiol (CBD) has presented anti-inflammatory, antioxidant, and neuroprotective properties.

METHODS

CMC, CS, and CBD were used and designed for three types of hydrogels (CMC/CS2/CBD, CMC/CS3/CBD, CMC/CS4/CBD) with different ratios of CMC and CS based on previous report and our preliminary experiments. The CMC/CS/CBD hydrogel was synthesized using electrostatic interaction without chemical crosslinking, characterized via fourier transform infrared (FT-IR), and tested for mechanical properties, swelling behavior, biocompatibility, antioxidant activity, cytotoxicity, and hemocompatibility. 60Co γ irradiation (5 Gy, 0.62 Gy/min) combined with 1 cm circular trauma was applied to establish RW mice model. Topical applications of CMC/CS3, CMC/CS2/CBD, CMC/CS3/CBD were used to treat RW injury once a day for 10 consecutive days. The mice were euthanized 7, 14, 21 days after radiation, and samples were collected.

RESULTS

FT-IR confirmed the successful formation of a polyelectrolyte network. The CMC/CS3/CBD hydrogel exhibited optimal mechanical strength, rapid gelation, high swelling capacity, and excellent biocompatibility. Both CMC/CS2/CBD and CMC/CS3/CBD hydrogels effectively improved RW injury 7, 14, 21 days after radiation. Reduced inflammation and increased collagen production were observed the two groups. The significant increased expression of interleukin (IL)-1β, IL-22, IL-17A, IL-6, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, CC motif chemokine ligand (CCL)2, CCL3, CCL4, CCL5, CCL11 in the RW group was greatly inhibited after treatment with CMC/CS3/CBD hydrogel. Transcriptome analysis revealed the hydrogel's impact on lipid metabolism and epithelial differentiation pathways.

CONCLUSIONS

By integrating CBD into a CMC/CS-based hydrogel without using toxic crosslinkers, this study provides a novel, biomaterial-based, biocompatible approach for RW injury. These findings pave the way for future clinical application of CMC/CS3/CBD hydrogel in RW injury.