Dual-action nasal spray with mussel protein and xylitol restores epithelial barrier and attenuates type 2 inflammation in allergic rhinitis

Allergic rhinitis (AR) is a prevalent chronic inflammatory disorder of the upper airways, driven by Th2-mediated immune dysregulation and compromised epithelial barrier function. Current therapies, such as intranasal corticosteroids, often exhibit limited efficacy and adverse effects upon prolonged use. Herein, we developed a novel dual-action nasal spray, termed Mefp, by combining mussel adhesive protein (MAP) and xylitol to simultaneously target epithelial barrier repair and inflammatory pathways. The Mefp formulation exhibited strong mucoadhesive properties, with nasal retention lasting up to 24 h, facilitated by catechol-mediated adhesion of 3,4-dihydroxyphenylalanine (DOPA) residues in MAP. In vitro experiments using LPS-stimulated human nasal epithelial cells (HNEpCs) demonstrated that Mefp significantly restored tight junction proteins (ZO-1 and occludin), suppressed NF-κB activation, reduced oxidative stress, and attenuated the release of pro-inflammatory (TNF-α, IL-6) and Th2 cytokines (IL-4, IL-5, IL-13). In an ovalbumin-induced murine AR model, Mefp treatment markedly alleviated allergic symptoms, reduced eosinophil infiltration, decreased OVA-specific IgE levels, and enhanced antioxidant enzyme activities. Histological and immunofluorescence analyses confirmed the restoration of mucosal integrity and tight junction assembly. Notably, Mefp demonstrated comparable or superior efficacy to mometasone furoate (MF) in alleviating allergic symptoms and suppressing key inflammatory mediators, while showing a better safety profile regarding epithelial integrity in vitro. These findings indicate that Mefp effectively addresses both epithelial barrier dysfunction and type 2 inflammation, offering a promising and safe therapeutic strategy for AR.