Pezato Rogerio, Singhera Gurpreet K, Guo Tony Ju Feng, Dorscheid Delbert R, Pascual Athenea, Thamboo Andrew
Division of Otolaryngology and Head and Neck Surgery, University of British Columbia, Vancouver, Canada.
Department of Otolaryngology and Head and Neck Surgery, Universidade Federal de São Paulo, São Paulo, Brazil.
Indian J Otolaryngol Head Neck Surg. 2025 Feb;77(2):905-912. doi: 10.1007/s12070-024-05291-6. Epub 2025 Jan 3.
Recent studies have demonstrated that corticosteroid delivered by nasal irrigation is superior to nasal spray in the treatment of chronic rhinosinusitis patients who have undergone sinus surgery. However, the local cytotoxicity of both delivery methods has not been previously evaluated. In this study we aimed to evaluate the cytotoxicity of corticosteroid prepared nasal irrigation solution and commercially available corticosteroid nasal spray.
Primary human nasal epithelial air-liquid interface 3D cultures established from nasal brushes from patients with nasal diseases with polyps, and healthy nasal mucosa ( = 6 each) were used to assess the cytotoxicity of different drug concentrations. The following drugs were screened: budesonide rinse, mometasone rinse, mometasone spray, fluticasone spray, azelastine/fluticasone spray, xylometazoline drops and benzalkonium chloride. Nasal epithelial cell characterization at passage zero was evaluated with β- Tubulin and FOXJ1 immunostaining as well as fluorescence-activated cell sorting using epithelial cell marker (EpCAM-488). To assess the drug induced cytotoxicity, an Alamar Blue assay, transepithelial electrical resistance and optical microscopy were applied.
Nasal irrigation using standard therapeutic concentrations of mometasone or budesonide demonstrated less cytotoxicity when compared to nasal spray of mometasone and fluticasone in stock concentration prescribed by the manufacturer. Nasal spray diluted by a factor of 10 demonstrated similar cytotoxicity to nasal irrigation using therapeutic concentration. This study reinforces the suspicion that it is not the drugs themselves but benzalkonium chloride that is the most involved in cytotoxicity.
Corticosteroid irrigation is less cytotoxic than corticosteroid spray to nasal epithelial cells.
最近的研究表明，对于接受鼻窦手术的慢性鼻-鼻窦炎患者，经鼻腔冲洗给予皮质类固醇优于鼻喷雾剂。然而，这两种给药方式的局部细胞毒性此前尚未得到评估。在本研究中，我们旨在评估皮质类固醇配制的鼻腔冲洗液和市售皮质类固醇鼻喷雾剂的细胞毒性。
使用从患有鼻息肉疾病的患者以及健康鼻黏膜的鼻刷建立的原代人鼻上皮气液界面3D培养物（每组各6个）来评估不同药物浓度的细胞毒性。筛选了以下药物：布地奈德冲洗液、莫米松冲洗液、莫米松喷雾剂、氟替卡松喷雾剂、氮卓斯汀/氟替卡松喷雾剂、赛洛唑啉滴鼻剂和苯扎氯铵。通过β-微管蛋白和FOXJ1免疫染色以及使用上皮细胞标志物（EpCAM-488）的荧光激活细胞分选来评估第0代鼻上皮细胞的特征。为了评估药物诱导的细胞毒性，应用了alamar蓝测定法、跨上皮电阻和光学显微镜检查。
与按照制造商规定的原液浓度使用莫米松和氟替卡松鼻喷雾剂相比，使用标准治疗浓度的莫米松或布地奈德进行鼻腔冲洗显示出较低的细胞毒性。稀释10倍的鼻喷雾剂显示出与使用治疗浓度的鼻腔冲洗相似的细胞毒性。本研究进一步证实了这样一种怀疑，即细胞毒性最主要涉及的不是药物本身，而是苯扎氯铵。
皮质类固醇冲洗对鼻上皮细胞的细胞毒性低于皮质类固醇喷雾。
