Preclinical in vitro evaluation of a new nasal formulation combining xylometazoline and hyaluronic acid: Permeability and penetration analysis using an advanced characterized human nasal model.

A new nasal formulation combining xylometazoline, a well-established nasal decongestant, and hyaluronic acid (HA) at a 3 mg/ml concentration and low-molecular-weight has been developed as a topical product intended for use in viral acute rhinosinusitis, with the aim of relieving nasal congestion and supporting epithelial integrity. HA, a moisturizing component of respiratory secretions, has been shown to promote epithelial integrity, stimulate mucociliary clearance and support wound healing. As part of the drug development process, this study investigated the permeation and penetration properties of xylometazoline and HA in the new formulation using a human nasal epithelium in vitro model. Results were compared to those of a xylometazoline mono-formulation and a well-established fixed-dose combination of xylometazoline and dexpanthenol. Morphological, ultrastructural and physiological analyses were performed to test nasal cells tolerability on prolonged drug exposure (6 h). HA in this new nasal formulation seems to be a component that exerts its effect mainly on the mucosal surface, which is the favoured site of action for topical products. HA was not detected in the basolateral compartment, consistent with retention at the mucosal surface. The results of our preclinical study do not indicate that the safety profile of xylometazoline would be altered by the addition of HA (or dexpanthenol). The barrier integrity of the in vitro human nasal epithelium was preserved across all tested formulations. Nanoparticle endocytosis was absent. These findings, obtained in a healthy in vitro nasal epithelial model, provide a valuable foundation for subsequent evaluation of this formulation in human clinical studies.