Acute viral rhinosinusitis (viral ARS), or commonly referred to as the “common cold”, is caused by respiratory viruses that cause disruption of the airway epithelial barrier and mucociliary dysfunction. Treatment of ARS is mainly symptomatic, with xylometazoline, a direct-acting α-adrenoceptor agonist, commonly used as a nasal decongestant. Unfortunately, this treatment does not resolve the epithelial dysfunction observed in ARS, and its use might negatively impact the nasal mucosa causing issues such as dryness, stinging, burning, rebound congestion, as well as atrophy. In light of this, a novel nasal spray formulation containing both xylometazoline and hyaluronic acid (HA) was developed to provide a more effective and safer treatment for viral ARS. HA is a natural polysaccharide known to hydrate and moisturise the upper respiratory tract, maintain the integrity of the nasal mucosa, and promote mucociliary clearance and wound healing. To investigate the potential of this combination, this study was conducted using the nasal MucilAirTMin vitro model and high-speed phase-contrast microscopy to examine the effect of xylometazoline and HA on ciliary function by measuring ciliary beat frequency and their cytotoxicity by morphological, histological and ultrastructural analysis. This research is the first to assess the effects of a specific dose and molecular weight of HA as an active pharmaceutical ingredient in nasal spray formulations. The combination of a fast-acting decongestant and an additional active agent targeting nasal epithelial dysfunction has the potential to provide an improved, reliable and safe treatment for viral ARS, and may serve as the basis for future clinical studies.
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