Innovative preclinical models for pulmonary drug delivery research.
Innovative preclinical models for pulmonary drug delivery research.
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DOI：
10.1080/17425247.2020.1730807
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发表时间：
2020-04
影响因子：
6.6
通讯作者：
Heuze-Vourc'h N
中科院分区：
文献类型：
--
作者：
Ehrmann S;Schmid O;Darquenne C;Rothen-Rutishauser B;Sznitman J;Yang L;Barosova H;Vecellio L;Mitchell J;Heuze-Vourc'h N
肺部给药是一个复杂的研究领域，它结合了驱动气溶胶传输和沉积的物理学和支撑吸入性药物疗效和毒性的生物学。可以实施无数的临床前方法，从硅胶内到体外、体外和体内。本文综述了气溶胶沉积的硅内数学和计算流体动力学模拟、用于估计药物输送和沉积的串级冲击器技术、先进的体外细胞培养方法及其相关的气溶胶暴露、芯片上肺技术、体外模拟、体内吸入性给药、肺成像和纵向药代动力学分析。不能提倡单一的临床前模式；所有方法从根本上来说都是互补的，应该根据好处和缺点来实施，以回答特定的科学问题。总体上最好的科学策略取决于正在研究的产品、吸入器设计、感兴趣的疾病、临床患者群体、先前的知识等。临床前测试不能从临床评估中分离出来，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会为临床前测试提供信息。这种转化性研究所需的专业知识范围不太可能在一个要求建立多国大型研究联合体的实验室中找到。
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. 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. No single pre-clinical 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. Pre-clinical 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 pre-clinical 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.
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DOI：
10.1089/089426804322994406
发表时间：
2004-03-01
期刊：
JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG
影响因子：
--
作者：
Esposito-Festen, JE;Ates, B;Tiddens, HAWM
通讯作者：
Tiddens, HAWM
影响因子：
3.7
作者：
Belser JA;Gustin KM;Katz JM;Maines TR;Tumpey TM
通讯作者：
Tumpey TM
影响因子：
3.8
作者：
Corley, Richard A.;Kabilan, Senthil;Einstein, Daniel R.
通讯作者：
Einstein, Daniel R.
影响因子：
3.3
作者：
DARQUENNE, C;PAIVA, M
通讯作者：
PAIVA, M
DOI：
10.1089/jamp.2017.1369
发表时间：
2018-02-01
影响因子：
3.4
作者：
Fioni, Alessandro;Selg, Ewa;Puccini, Paola
通讯作者：
Puccini, Paola