Protective effects of sodium hyaluronate nasal spray on murine nasal mucosa via preservation of airway surface liquid and mucociliary clearance

Background Saline nasal irrigation is widely used in the management of nasal diseases; however, its inability to replicate the physicochemical properties of airway surface liquid (ASL) may limit its long-term efficacy. We aimed to investigate the protective mechanisms of sodium hyaluronate (hyaluronic acid, HA) nasal spray on the nasal mucosa and to compare its effects with conventional saline. Methods BALB/c mice were subjected to intranasal mugwort allergen exposure and treated with either saline or sodium hyaluronate nasal spray for 1–7 days. Behavioral assessments and nasal crusting scores were recorded. Cytokine levels (IL-4, IL-25, IL-33, TSLP) were quantified using ELISA. Histological analyses (H&E, PAS, Alcian Blue) and immunohistochemistry (ZO-1, Occludin) were performed. Ex vivo mucociliary clearance (MCC) was assessed under different liquid environments. Results HA treatment significantly reduced nasal scratching and attenuated crust formation following prolonged allergen exposure. This was accompanied by suppression of Th2 cytokines and epithelial-derived alarmins in both nasal mucosa and serum. HA preserved mucus layer thickness and goblet cell density and significantly delayed the decline in MCC. Tight junction protein expression remained unchanged. Conclusion Sodium hyaluronate nasal spray confers mucosal protection primarily through preservation of ASL homeostasis and MCC function rather than modulation of epithelial tight junctions. These findings highlight HA as a promising alternative to saline for long-term management of nasal mucosal disorders.