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.
Keywords: PBPK modeling; biodistribution; computational nanotoxicology; endocytosis; nanomaterials; phagocytosis; physiologically based pharmacokinetic modeling; toxicokinetics.