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.

中文翻译：

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用简单的高速显微镜测量的体外人鼻上皮的纤毛搏动频率可用于鼻用药物制剂的安全性研究。

鼻用药物制剂可有效地将治疗药物局部递送至鼻窦粘膜或通过直接吸收入血流来全身性递送药物。潜在的鼻部治疗方法的增长领域包括鼻腔接种疫苗，甚至治疗神经退行性疾病。但是，重要的是，鼻用药物制剂对鼻上皮的纤毛和粘膜不具有破坏作用。粘膜纤毛清除代表呼吸道的第一个宿主防御，需要协调地殴打纤毛。确定粘膜纤毛清除率的关键参数是纤毛搏动频率（CBF）。这项研究的目的是验证在鼻腔MucilAir™体外模型中进行CBF测量的高速数字成像，并测试其在进行电子毒性研究以评估鼻用药物制剂安全性方面的潜力。我们的CBF测量设置首先通过苯扎氯铵（一种具有纤溶抑制作用的常用防腐剂）进行了验证。接下来，用莫米松鼻喷雾剂（Mommox®/ MometasoneSandoz®）处理MucilAir™模型。证实了莫米松鼻喷雾剂的短期纤毛刺激作用和剂量依赖性作用。后处理分析显示MucilAir™模型的超微结构未改变。结论，