Ciliary beat frequency of in vitro human nasal epithelium measured with the simple high-speed microscopy is applicable for safety studies of nasal drug formulations

Abstract

Nasal drug formulations can be effective for local delivery of therapeutic drugs to the sinonasal mucosa or for systemic drug delivery by absorption directly into the bloodstream. The growing field of potential nasal therapies includes nasal vaccination and even treatment of neurodegenerative diseases. However, it is important that nasal drug formulations don't have a disruptive effect on the cilia and mucosa of nasal epithelium. Mucociliary clearance represents the first host defence of the respiratory tract that requires the coordinated beating of cilia. A key parameter to determine mucociliary clearance is ciliary beat frequency (CBF). The objective of this study was to validate the high-speed digital imaging for CBF measurements in nasal MucilAir™ in vitro model and to test its potential for ciliotoxicity studies to evaluate the safety of investigational nasal drug formulations. Our CBF measuring setup was first validated by benzalkonium chloride, a common-practice preservative with cilio-inhibiting effect. Next, MucilAir™ model was treated with mometasone nasal spray (Mommox®/Mometasone Sandoz®). Short term cilio-stimulatory effect and dose dependent effect of mometasone nasal spray were demonstrated. Post-treatment analysis showed un-altered ultrastructure of MucilAir™ model. In conclusion, characterization of the ciliary activity of nasal MucilAir™ in vitro model and its response to relevant agents with herein developed efficient and reproducible set up for CBF analysis show great potential of this model for airway ciliotoxicity studies.

Keywords: Ciliary beat frequency; Drug safety; Mucociliary clearance; Nasal drug formulations; Nasal in vitro model; Ultrastructural analysis.