Starpharma Pty Ltd, Abbotsford, VIC, 3067, Australia.
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92307, USA.
Sci Rep. 2024 Sep 11;14(1):21259. doi: 10.1038/s41598-024-72262-w.
COVID-19 remains a severe condition for many including immunocompromised individuals. There remains a need for effective measures against this and other respiratory infections, which transmit via virus-laden droplets that reach the nasal or oral mucosae. Nasal sprays offer potential protection against viruses. Such formulations should preserve normal nasal mucociliary function. The antiviral barrier efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were evaluated and compared with other available nasal sprays-low pH hydroxypropyl methylcellulose (HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). Assays simulated clinical conditions. Antiviral barrier function and cell viability were assessed in airway cell monolayers, while a model of fully differentiated human nasal epithelium (MucilAir™) was utilized to evaluate tissue integrity, cytotoxicity, cilia beating frequency, and mucociliary clearance. AS-NS reduced infectious virus in cell monolayers and demonstrated a benign cytotoxicity profile. In human nasal epithelium ex vivo, AS-NS had no impact on mucociliary function (cilia beating nor mucociliary clearance). Carr-NS, HPMC-NS, NO-NS and PI-NS demonstrated limited antiviral effects, while HPMC-NS caused inhibition of mucociliary function. Astodrimer sodium nasal spray demonstrates an acceptable nonclinical efficacy and safety profile as a barrier nasal spray against respiratory viral infection in the nasal cavity.
对于许多人来说，包括免疫功能低下的个体，COVID-19 仍然是一种严重的疾病。仍然需要有效的措施来对抗这种疾病和其他呼吸道感染，这些感染通过携带病毒的飞沫传播，这些飞沫会到达鼻腔或口腔黏膜。鼻腔喷雾剂为病毒提供了潜在的保护。这种制剂应保持正常的鼻腔粘液纤毛功能。本研究评估并比较了阿司特罗姆钠鼻腔喷雾剂（AS-NS）与其他市售鼻腔喷雾剂（低 pH 羟丙基甲基纤维素（HPMC-NS）、iota-卡拉胶（Carr-NS）、一氧化氮（NO-NS）和聚维酮碘（PI-NS）的抗病毒屏障功效和对粘液纤毛功能的影响。这些试验模拟了临床条件。在气道细胞单层中评估了抗病毒屏障功能和细胞活力，同时利用完全分化的人鼻腔上皮模型（MucilAir™）评估组织完整性、细胞毒性、纤毛摆动频率和粘液纤毛清除率。AS-NS 减少了细胞单层中的感染性病毒，并表现出良性的细胞毒性特征。在人体鼻腔上皮组织中，AS-NS 对粘液纤毛功能（纤毛摆动和粘液纤毛清除率）没有影响。Carr-NS、HPMC-NS、NO-NS 和 PI-NS 显示出有限的抗病毒作用，而 HPMC-NS 抑制了粘液纤毛功能。阿司特罗姆钠鼻腔喷雾剂作为鼻腔内呼吸道病毒感染的屏障鼻腔喷雾剂，具有可接受的非临床疗效和安全性。
