A Lithium-Containing Hydrogel for Topical Prevention of Radiation-Induced Oral Mucositis and Dysgeusia

Radiation-induced oral mucositis (RIOM) and taste dysfunction (dysgeusia) are common complications of radiotherapy in cancer patients. Current clinical interventions for RIOM mainly focus on symptom alleviation but with limited efficacy and nonevidenced taste protection. Our previous study showed that systemic administration of lithium (a Wnt agonist) ameliorated radiation-induced oral mucositis and dysgeusia by promoting basal cell proliferation and taste bud renewal. However, the potential cytotoxicity of systemic administration of lithium necessitates topical application. In this study, a poly(vinyl alcohol)-lithium citrate (PVA-LC) hydrogel was developed, which promoted the substantivity of lithium in the moist and dynamic oral cavity with a good biocompatibility. The hydrogel significantly alleviated RIOM, as shown by the decrease in the proportion of ulcer area from 37.09% (±5.58%) to 0.54% (±0.40%), and protected taste perception in mice. Mechanistically, lithium citrate (Li₃C₆H₅O₇) effectively blocked X-ray-induced apoptosis and promoted cell proliferation and migration, which were crucial for the reconstitution of oral mucosa. In summary, the current study developed a lithium-containing mucoadhesive hydrogel, showing good clinical translational potential in the management of radiotherapy-associated oral complications.