School of Pharmacy, The Faculty of Medical Sciences, King George VI Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.
Division of Stratified Medicine, Biomarkers & Therapeutics, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Nanomedicine (Lond). 2018 May;13(9):973-975. doi: 10.2217/nnm-2018-0064. Epub 2018 May 23.
Adverse infusion reactions to regulatory approved nanomedicines in human subjects are idiosyncratic, but outwardly reproducible in pigs. A large body of evidence suggests that the porcine reactions are related to robust nanoparticle clearance by pulmonary intravascular macrophages (PIMs), and rapid release of arachidonate metabolites from these cells. Similar to pigs, other animals that have resident PIMs in their lungs also respond to intravenously injected particles, where rapid particle clearance by PIMs correlate with peak periods of cardiopulmonary distress. Normal human lungs, however, do not have PIMs, but 'induced' PIMs have been identified in pulmonary circulation under certain pathological conditions. We question suitability, and limitation of these preclinical models for global assessment of nanomedicine safety, and discuss alternative models and approaches.
在人体中，监管批准的纳米药物的不良输注反应是特有的，但在猪身上可以重现。大量证据表明，猪的反应与肺血管内巨噬细胞（PIMs）对纳米颗粒的强大清除作用以及这些细胞中花生四烯酸代谢物的快速释放有关。与猪类似，其他肺部有常驻 PIMs 的动物也会对静脉内注射的颗粒产生反应，其中 PIMs 对颗粒的快速清除与心肺窘迫的高峰期相关。然而，正常的人类肺部没有 PIMs，但在某些病理条件下，在肺循环中已经鉴定出“诱导”的 PIMs。我们质疑这些临床前模型对纳米药物安全性进行全球评估的适用性和局限性，并讨论了替代模型和方法。
