Development of a doxepin-loaded chitosan nanogel as an innovative nano platform for oral mucositis treatment

Oral mucositis is a prevalent complication in patients undergoing chemotherapy. This study aimed to develop and characterize a doxepin-loaded chitosan nanogel (DX-CN) as a topical treatment option. DX-CN and chitosan nanogel (CN) were synthesized using ionic gelation and characterized by Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM). FTRI confirmed the spectral compatibility of DX-CN. The nanogels exhibited spherical morphology. Particle sizes were 322.7 nm for DX-CN and 302.8 nm for CN. Polydispersity indices (PdI) were 0.732 for DX-CN and 0.51 for CN. Zeta potentials (ZP) were +52.7 mV for DX-CN and +52.8 mV for CN. In vitro assays included drug loading capacity (96.2 % for DX-CN), drug release profile (83.39 % cumulative release over 10 h), cytotoxicity, and antioxidative effects. DX-CN exhibited significant cytocompatibility with human umbilical vein endothelial cells (HUVEC) and selective cytotoxicity against oral squamous cell carcinoma (OSCC) cells. Furthermore, DX-CN demonstrated reduced oxidative stress, as indicated by lower lipid peroxidation, lactate dehydrogenase leakage, and reactive oxygen species formation compared to doxepin alone. The findings suggest that DX-CN, with its efficient drug loading, sustained release, and targeted biocompatibility, holds promise as a therapeutic platform for the topical treatment of chemotherapy-induced oral mucositis.