一种用于评估金纳米颗粒的种间药代动力学、暴露和毒性的计算框架。
A computational framework for interspecies pharmacokinetics, exposure and toxicity assessment of gold nanoparticles.
机构信息
Institute of Computational Comparative Medicine (ICCM), Kansas State University, Manhattan, KS 66506, USA.
Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS 66506, USA.
出版信息
Nanomedicine (Lond). 2016 Jan;11(2):107-19. doi: 10.2217/nnm.15.177. Epub 2015 Dec 11.
AIM
To develop a comprehensive computational framework to simulate tissue distribution of gold nanoparticles (AuNP) across several species.
MATERIALS & METHODS: This framework was built on physiologically based pharmacokinetic modeling, calibrated and evaluated with multiple independent datasets.
RESULTS
Rats and pigs seem to be more appropriate models than mice in animal-to-human extrapolation of AuNP pharmacokinetics and that the dose and age should be considered. Incorporation of in vitro and/or in vivo cellular uptake and toxicity data into the model improved toxicity assessment of AuNP.
CONCLUSION
These results partially explain the current low translation rate of nanotechnology-based drug delivery systems from mice to humans. This simulation approach may be applied to other nanomaterials and provides guidance to design future translational studies.
目的
开发一种综合的计算框架,以模拟金纳米粒子(AuNP)在多个物种中的组织分布。
材料与方法
该框架建立在基于生理学的药代动力学模型基础上,并用多个独立数据集进行了校准和评估。
结果
在将 AuNP 药代动力学从动物外推到人体时,大鼠和猪似乎比小鼠更适合作为模型,并且应考虑剂量和年龄因素。将体外和/或体内细胞摄取和毒性数据纳入模型可以改善 AuNP 的毒性评估。
结论
这些结果部分解释了当前基于纳米技术的药物输送系统从小鼠到人体的低转化率。这种模拟方法可应用于其他纳米材料,并为设计未来的转化研究提供指导。