呼吸肺芯片:一种多功能工具,用于评估多种治疗方式的呼吸毒性
Linnea Johansson1,2, Giulia Raggi3, James Cartwright4
1Biopharma Safety, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Archives of toxicology
|January 14, 2026
概括
AlveoliX Lung-on-Chip模型有效地预测了吸入药物的呼吸道毒性,优于2D培养. 这种先进的模型可以识别炎症潜力,并有助于开发更安全的呼吸道疾病治疗方法.
科学领域:
- 毒理学 毒理学 毒理学
- 在体外模型模型.
- 呼吸系统药物 呼吸系统药物
背景情况:
- 吸入药物输送直接针对呼吸道疾病.
- 候选药物开发面临由于体内肺毒性发现的局限性.
- 需要预测性体外模型来评估肺毒性和炎症反应.
研究的目的:
- 评估 AlveoliX Lung-on-Chip (AX Lung-on-Chip) 模型对吸入物质呼吸系统毒性的预测准确度.
- 为了比较AX Lung-on-Chip模型的性能与传统的二维细胞培养.
- 评估模型根据炎症潜力区分化合物的能力.
主要方法:
- 利用AX Lung-on-Chip模型和2D细胞培养来测试八种吸入的物质.
- 使用二维培养优化剂量和研究设计.
- 在AX Lung-on-Chip模型中纳入多个终点和机械拉伸,以提高灵敏度.
主要成果:
- 2D培养不能根据炎症潜力区分化合物.
- AX Lung-on-Chip模型显示出更明显的反应和基于炎症潜力的差异化化合物.
- 在AX Lung-on-Chip模型中的机械拉伸可能会增加对细胞因子反应的敏感性.
- 该模型准确地预测了 in vivo 药物诱导的炎症反应,涉及多种肺病理.
结论:
- AX Lung-on-Chip模型显示了对吸入化合物的呼吸系统毒性有显著的预测能力.
- 这种模型在评估炎症潜力和毒性方面超过了二维培养.
- AX Lung-on-Chip为识别吸入化合物的毒性和推进更安全的药物开发提供了一个有希望的工具.
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