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ISSN Online: 2377-424X

ISBN Print: 978-1-56700-474-8

ISBN Online: 978-1-56700-473-1

International Heat Transfer Conference 16
August, 10-15, 2018, Beijing, China

Physiologically-based pharmacokinetic modeling of different size polyethylene glycol-coated gold nanoparticles in mice

Get access (open in a dialog) DOI: 10.1615/IHTC16.nmt.023362
pages 7025-7032

Résumé

Background: Nanoparticles (NPs) are the important ingredients of air pollution and widely used in the field of nanotechnology, which increase the health risk of both intentional and unintentional exposure. The NPs size plays a key role in their dynamic interaction with the biological system. However, the effect of particle size on biodistribution and pharmacokinetics of NPs are not clear.
Objectives: To investigate the biodistribution of intravenously injected different size pegylated AuNPs in mice and human using physiologically based pharmacokinetic (PBPK) model.
Methods: The PBPK model was developed to explore biodistribution of AuNPs. We considered the role of endocytosis mechanism in plasma and tissues. In addition, the size-dependent permeability coefficient, excretion rate constant, phagocytic capacity, uptake rate and release rate were derived.
Results: AuNPs were primarily distributed in plasma, liver and spleen regardless of particle size, and almost all captured by the phagocytes in liver and spleen, while few was captured in plasma; smaller AuNPs showed the most widespread organ distribution and longer circulation time; the results also showed that the accumulation of AuNPs decreased with increasing size in most organs and plasma, while the accumulation of AuNPs showed an inverted U-shaped curve in liver. Size, partition coefficients and body weight were the key factors influencing the organ distribution of AuNPs.
Conclusions: This study revealed that the distribution and accumulation of AuNPs in various organs are size-dependent for smaller AuNPs. A better understanding of these mechanisms could provide effective guides for the design of NPs and drug delivery.