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Nanomedicine (Lond). 2016 Jan;11(2):107-19. doi: 10.2217/nnm.15.177. Epub 2015 Dec 11.

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

Author information

1
Institute of Computational Comparative Medicine (ICCM), Kansas State University, Manhattan, KS 66506, USA.
2
Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS 66506, USA.
3
Department of Radiology, University of Missouri, Columbia, MO 65211, USA.

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.

KEYWORDS:

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

PMID:
26653715
DOI:
10.2217/nnm.15.177
[Indexed for MEDLINE]
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