Abstract
Certain active drugs and excipients of nasal formulations may impair ciliary function and mucociliary clearance. The ciliary beat frequency (CBF) is a key parameter for determining mucociliary clearance rate, and in vitro assessments of CBF have proven to be accurate and reproducible. Since topical nasal formulations are applied with repeated doses, it is essential to elucidate their chronic, as opposed to acute, effect on mucociliary clearance and nasal mucosa. The aim of this study was to assess for the first time the ciliotoxicity and cytotoxicity of nasal sprays intended for chronic treatment (with repeated doses) using a previously designed set-up for CBF measurements. For 2 weeks, the 3D nasal MucilAir™ in vitro models were treated daily with undiluted or clinically relevant doses of mometasone nasal spray, placebo nasal spray, culture medium, or they were untreated. We demonstrated a dose-dependent and time-dependent (cumulative) effect of the nasal sprays on ciliary activity and cytotoxicity using CBF measurements and ultrastructural analysis, respectively. Our results indicate that repeated administration of clinically relevant doses of mometasone nasal spray is safe for in vivo use, which is in good agreement with a previous clinical study. Overall, our study suggests that such in vitro assays have great potential for topical nasal drug screening.
Highlights
Intranasal decongestants, corticosteroids, antihistamines, and anticholinergics are commonly used topical nasal drugs that are often suggested as first-line therapy for nasal conditions such as congestion, rhinitis, sinusitis, and related allergic or chronic nasal conditions [1,2,3,4,5,6]
Our results indicate that repeated administration of clinically relevant doses of mometasone nasal spray is safe for in vivo use, which is in good agreement with a previous clinical study
We have previously shown that single-exposure treatment with undiluted mometasone nasal spray for 3 h increases ciliary activity of nasal MucilAirTM in vitro models by 25.7 ± 2.5% compared to culture medium-treated controls
Summary
Intranasal decongestants, corticosteroids, antihistamines, and anticholinergics are commonly used topical nasal drugs that are often suggested as first-line therapy for nasal conditions such as congestion, rhinitis, sinusitis, and related allergic or chronic nasal conditions [1,2,3,4,5,6]. They are administered as lavages, drops, squirt systems, or sprays and are used as repeated-dose treatments for nasal diseases [2,7]. The mechanical barrier against pathogen invasion consists of intracellular junctions, mucus, and mucociliary clearance, which depends on the ciliary activity and mucus production of ciliated and goblet cells, respectively [8]
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