A computational framework for interspecies pharmacokinetics, exposure and toxicity assessment of gold nanoparticles

Abstract

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.