Multifunctional tetramethylpyrazine-loaded carbomer gel for cutaneous radioprotection against radiation dermatitis

Background Radiation-induced dermatitis represents a common adverse reaction following tumor radiotherapy, and effective prophylactic and therapeutic approaches remain limited. Tetramethylpyrazine (TMP) exhibits promising anti-inflammatory and antioxidant properties. Nevertheless, its poor skin retention and incompletely elucidated molecular mechanisms targeting radiation-induced dermatitis restrict its clinical utility. As a clinically-approved pharmaceutical excipient, Carbopol® 940 imparts desirable skin-adhesive characteristics to gel formulations. Methods In this study, a TMP-loaded functional Carbopol® 940 gel (TMP-gel) with favorable translational potential was developed. Its therapeutic efficacy and underlying molecular mechanisms for alleviating radiation-induced dermatitis were systematically evaluated. Results In vitro cellular assays demonstrated that TMP-gel triggers the Nrf2 antioxidant cascade, suppresses NF-κB-mediated pro-inflammatory signaling, and inhibits pathological over-activation of Wnt/β-catenin signal transduction. In vivo experiments confirmed the potent therapeutic activity of the gel against radiation-induced dermatitis. Conclusion This multifunctional tetramethylpyrazine-loaded carbomer gel provides a novel biomedical platform enabling non-invasive concurrent prevention and intervention for radiation-provoked skin injury during tumor radiotherapy.