PuSH - Publication Server of Helmholtz Zentrum München: Development of a multi-route physiologically based pharmacokinetic (PBPK) model for nanomaterials: A comparison between a traditional versus a new route-specific approach using gold nanoparticles in rats.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Chou, W.C.* ; Cheng, Y.H.* ; Riviere, J.E.* ; Monteiro-Riviere, N.A.* ; Kreyling, W.G. ; Lin, Z.*

Development of a multi-route physiologically based pharmacokinetic (PBPK) model for nanomaterials: A comparison between a traditional versus a new route-specific approach using gold nanoparticles in rats.

Part. Fibre Toxicol. 19:47 (2022)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

BACKGROUND: Physiologically based pharmacokinetic (PBPK) modeling is an important tool in predicting target organ dosimetry and risk assessment of nanoparticles (NPs). The methodology of building a multi-route PBPK model for NPs has not been established, nor systematically evaluated. In this study, we hypothesized that the traditional route-to-route extrapolation approach of PBPK modeling that is typically used for small molecules may not be appropriate for NPs. To test this hypothesis, the objective of this study was to develop a multi-route PBPK model for different sizes (1.4-200 nm) of gold nanoparticles (AuNPs) in adult rats following different routes of administration (i.e., intravenous (IV), oral gavage, intratracheal instillation, and endotracheal inhalation) using two approaches: a traditional route-to-route extrapolation approach for small molecules and a new approach that is based on route-specific data that we propose to be applied generally to NPs. RESULTS: We found that the PBPK model using this new approach had superior performance than the traditional approach. The final PBPK model was optimized rigorously using a Bayesian hierarchical approach with Markov chain Monte Carlo simulations, and then converted to a web-based interface using R Shiny. In addition, quantitative structure-activity relationships (QSAR) based multivariate linear regressions were established to predict the route-specific key biodistribution parameters (e.g., maximum uptake rate) based on the physicochemical properties of AuNPs (e.g., size, surface area, dose, Zeta potential, and NP numbers). These results showed the size and surface area of AuNPs were the main determinants for endocytic/phagocytic uptake rates regardless of the route of administration, while Zeta potential was an important parameter for the estimation of the exocytic release rates following IV administration. CONCLUSIONS: This study suggests that traditional route-to-route extrapolation approaches for PBPK modeling of small molecules are not applicable to NPs. Therefore, multi-route PBPK models for NPs should be developed using route-specific data. This novel PBPK-based web interface serves as a foundation for extrapolating to other NPs and to humans to facilitate biodistribution estimation, safety, and risk assessment of NPs.

Impact Factor

Scopus SNIP

Altmetric

9.112

0.000