A novel chitosan-based doxepin nano-formulation for chemotherapy-induced oral mucositis: A randomized, double-blinded, placebo-controlled clinical trial

Abstract Objectives Considering the prevalence of oral mucositis, we aimed to use the analgesic effects of doxepin with antimicrobial and bio-adhesive nature of chitosan to fabricate a nano-formulation for treatment of chemotherapy-induced oral mucositis. Materials and Method Nanogel was fabricated via ionic gelation and characterized. Sixty patients were randomly divided and received four different treatments for 14 days: diphenhydramine + aluminum-magnesium mouthwash (control), doxepin mouthwash (DOX MW), chitosan nanogel (CN), and doxepin/chitosan nanogel (CN + DOX). Lesions were assessed with four indices, national cancer institute (NCI), world health organization (WHO), and corld conference on clinical and research in nursing (WCCNR) and visual analogue scale (VAS) before and 3, 7, and 14 days after interventions. Kruskal Wallis test was used for pairwise comparison. Results CN had semisolid consistency, uniform spherical shape, an average size of 47.93 ± 21.69 nm and a zeta potential of + 1.02 ± 0.16 mV. Three days after intervention CN + DOX reduced WHO, WCCNR and VAS scores significantly more than control. Seven days after intervention CN + DOX reduced NCI and WCCNR significantly more than control; and it reduced WCCNR significantly more than CN. Fourteen days after intervention CN + DOX reduced NCI significantly more than control. Conclusion Chitosan-based doxepin nano-formulation might be a promising alternative for routine treatments of oral mucositis.