The semi-interpenetrating network hydrogel loaded with Oridonin and DNase-I on healing of chemoradiotherapy-induced oral mucositis

Oral mucositis (OM) is a common side effect experienced by cancer patients undergoing chemotherapy and/or radiotherapy. In this study, we developed a semi-interpenetrating network hydrogel (IPN) that is suitable for adhesion to oral mucous membranes and gradual degradation in the oral environment. This IPN was based on the combination of ε-polylysine (PLL) and Hetastarch (HES), loaded with DNase-I and Oridonin (ORI) (ORI/DNase-I/IPN) for the treatment of OM. In vitro studies were conducted to evaluate degradation, adhesion, release analysis, as well as bioactivity including cell proliferation and wound healing assays using epidermal keratinocyte and fibroblast cell lines. Furthermore, the therapeutic effects of ORI/DNase-I/IPN were investigated in vivo using Sprague-Dawley (SD) rats with chemoradiotherapy-induced OM. The results demonstrated that the IPN exhibited excellent adhesion to wet mucous membranes, and the two drugs co-encapsulated in the hydrogel were released in a controlled manner. The in vivo wound repair effect, microbiological assays, H&E and Masson staining supported the non-toxicity of ORI/DNase-I/IPN, as well as its ability to accelerate the healing of oral ulcers and reduce inflammation. Overall, ORI/DNase-I/IPN demonstrated a therapeutic effect on oral ulcers in rats by significantly accelerating the healing process and reducing inflammation. These findings provide new insights into possible therapies for OM.