Comprehensive evaluation of xylometazoline hydrochloride formulations: Ex-vivo and in-vitro studies

Abstract

Xylometazoline is a well-established nasal decongestant that has been used alone and in combination with dexpanthenol as an over the counter (OTC) medicine. Considering the possibility of further improvement of xylometazoline nasal formulations, hyaluronic acid (HA) was evaluated as an additional ingredient. The aim of this study was to investigate the permeation, mucosal retention, and mucoadhesion properties of a new xylometazoline-HA [Xylo-HA] formulation ex vivo and to explore the potential benefits of incorporating HA in the formulation in vitro. Sheep nasal mucosa was used in the ex vivo study, where Xylo-HA was compared with xylometazoline alone [Xylo-Mono], and in combination with dexpanthenol [Xylo-Dex] to understand the impact of formulation changes. The permeation of xylometazoline was generally low (Xylo-Mono 11.14 ± 4.75 %, Xylo-HA 14.57 ± 5.72 % and Xylo-Dex 11.00 ± 3.05 % of the applied dose). The steady state fluxes of xylometazoline were determined as 12.64 ± 3.52 μg/cm²h, 14.94 ± 3.38 μg/cm²h and 12.19 ± 2.05 μg/cm²h for Xylo-Mono, Xylo-HA and Xylo-Dex, respectively. No significant differences were observed between the formulations in the permeation nor mucosal retention studies (p > 0.05 for all), while Xylo-HA exhibited superior mucoadhesive proprieties (p < 0.05 for all). The effects on wound healing and barrier integrity of the three xylometazoline formulations were tested in vitro on HaCaT cells. To better elucidate the role of HA, an additional HA formulation without xylometazoline was prepared (HA-Mono). A scratch test was performed to evaluate wound healing, revealing that the test formulations did not achieve complete wound closure within 72 h and demonstrated a similar effect at the end of the testing period. To assess the effect on barrier integrity, cells were treated for 5 days with daily measurements of transepithelial electrical resistance (TEER). At the end of the experiment, Xylo-Dex showed a moderate 14 % increase in TEER, while Xylo-Mono did not significantly affect this parameter. TEER rose by 951 % in the Xylo-HA, and by 10497 % in the HA group, suggesting that incorporating HA led to enhanced barrier function. Further clinical studies are recommended to better understand the clinical implications and efficacy of the Xylo-HA formulation, with particular focus on the role of HA.