Introduction: Pulmonary drug delivery is a complex field of research combining physics which drive aerosol transport and deposition and biology which underpins efficacy and toxicity of inhaled drugs. A myriad of preclinical methods, ranging from in-silico to in-vitro, ex-vivo and in-vivo, can be implemented.Areas covered: The present review covers in-silico mathematical and computational fluid dynamics modelization of aerosol deposition, cascade impactor technology to estimated drug delivery and deposition, advanced in-vitro cell culture methods and associated aerosol exposure, lung-on-chip technology, ex-vivo modeling, in-vivo inhaled drug delivery, lung imaging, and longitudinal pharmacokinetic analysis.Expert opinion: No single preclinical model can be advocated; all methods are fundamentally complementary and should be implemented based on benefits and drawbacks to answer specific scientific questions. The overall best scientific strategy depends, among others, on the product under investigations, inhalation device design, disease of interest, clinical patient population, previous knowledge. Preclinical testing is not to be separated from clinical evaluation, as small proof-of-concept clinical studies or conversely large-scale clinical big data may inform preclinical testing. The extend of expertise required for such translational research is unlikely to be found in one single laboratory calling for the setup of multinational large-scale research consortiums.

中文翻译：

---

用于肺部药物输送研究的创新临床前模型。


简介：肺部药物输送是一个复杂的研究领域，结合了驱动气溶胶运输和沉积的物理学和支撑吸入药物的功效和毒性的生物学。可以实施多种临床前方法，从计算机到体外、离体和体内。涵盖领域：本综述涵盖气溶胶沉积、级联冲击器的计算机数学和计算流体动力学模型估计药物输送和沉积的技术、先进的体外细胞培养方法和相关的气溶胶暴露、肺芯片技术、离体建模、体内吸入药物输送、肺部成像和纵向药代动力学分析。专家意见：不能提倡单一的临床前模型；所有方法从根本上都是互补的，应根据优缺点来实施，以回答具体的科学问题。总体最佳科学策略取决于所研究的产品、吸入装置设计、感兴趣的疾病、临床患者群体、先前的知识等。临床前测试不应与临床评估分开，因为小型概念验证临床研究或相反的大规模临床大数据可能为临床前测试提供信息。此类转化研究所需的专业知识不太可能在一个需要建立跨国大型研究联盟的实验室中找到。