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

To develop a comprehensive computational framework to simulate tissue distribution of gold nanoparticles (AuNP) across several species.

This framework was built on physiologically based pharmacokinetic modeling, calibrated and evaluated with multiple independent datasets.

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.

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.