Multifunctional xylitol-HA hydrogel for chronic rhinosinusitis management

Purpose: Chronic rhinosinusitis (CRS) often recurs after surgery due to biofilms and inflammation, as current therapies have poor mucosal retention and limited biofilm penetration. We developed a natural hydrogel combining xylitol and hyaluronic acid (HA) to enhance drug delivery and antibiofilm efficacy.

Methods: A hydrogel of xylitol (5% w/v) and HA (0.1% w/v), with or without mometasone furoate (MF, 0.2 mg/mL), was formulated. Mucoadhesion was tested in mice. Biocompatibility, anti-inflammatory effects (IL-6, IL-8, TNF-α, FOXJ1), and ciliary toxicity were evaluated in LPS-stimulated human nasal epithelial cells (HNEpCs). Antibiofilm activity against S. aureus, P. aeruginosa, and S. pneumoniae was assessed via MIC/MBC, crystal violet staining, and SEM. Virulence gene expression (fnbA, fnbB, clfB, sarA, agrA) was analyzed during HNEpC-S. aureus co-culture.

Results: The xylitol-HA hydrogel showed prolonged nasal retention (up to 12 h). MF incorporation further improved mucoadhesion. The xylitol-HA-MF formulation was biocompatible, significantly reduced IL-6, IL-8, and TNF-α, and partially restored LPS-suppressed FOXJ1 expression (p < 0.01). MF addition provided synergistic bactericidal activity (MBC: 32-64 μg/mL) and reduced pre-formed biofilm biomass (p < 0.05). It also downregulated S. aureus adhesion genes and global regulators (p < 0.01).

Conclusions: A natural xylitol-based hydrogel with MF offers prolonged mucosal retention, potent anti-inflammatory effects, and synergistic antibiofilm activity by targeting Bacterial virulence, presenting a promising strategy for postoperative CRS management.