Modelling the biodistribution of inhaled gold nanoparticles in rats with interspecies extrapolation to humans.

The increasing intentional and non-intentional exposure to nanoparticles (NPs) has raised the interest concerning their fate and biodistribution in the body of animals and humans after inhalation. In this context, Physiologically Based (pharmaco)Kinetic (PBK) modelling has emerged as an in silico approach that simulates the biodistribution kinetics of NPs in the body using mathematical equations. Due to restrictions in data availability, such models are first developed for rats or mice. In this work, we present the interspecies extrapolation of a PBK model initially developed for rats, in order to estimate the biodistribution of inhaled gold NPs (AuNPs) in humans. The extrapolation framework is validated by comparing the model results with experimental data from a clinical study performed on humans for inhaled AuNPs of two different sizes, namely 34 nm and 4 nm. The novelty of this work lies in the extrapolation of a PBK model for inhaled AuNPs to humans and comparison with clinical data. The extrapolated model is in good agreement with the experimental data, and provides insights for the mechanisms of inhaled AuNP translocation to the blood circulation, after inhalation. Finally, the biodistribution of the two sizes of AuNPs in the human body after 28 days post-exposure is estimated by the model and discussed.