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Translocation of gold nanoparticles across the lung epithelial tissue barrier: Combining in vitro and in silico methods to substitute in vivo experiments

  • Bachler, Gerald ETH Zürich, Institute for Chemical and Bioengineering, Zürich, Switzerland - University of Fribourg, Adolphe Merkle Institute, Fribourg, 1700, Switzerland
  • Losert, Sabrina ETH Zürich, Institute for Chemical and Bioengineering, Zürich, Switzerland - EMPA, Swiss Federal Laboratories for Material Science and Technology, Dübendorf, Switzerland
  • Umehara, Yuki University of Fribourg, Adolphe Merkle Institute, Fribourg, 1700, Switzerland
  • Goetz, Natalie von ETH Zürich, Institute for Chemical and Bioengineering, Zürich, Switzerland
  • Rodriguez-Lorenzo, Laura University of Fribourg, Adolphe Merkle Institute, Fribourg, 1700, Switzerland
  • Petri-Fink, Alke University of Fribourg, Adolphe Merkle Institute, Fribourg, 1700, Switzerland
  • Rothen-Rutishauser, Barbara University of Fribourg, Adolphe Merkle Institute, Fribourg, 1700, Switzerland
  • Hungerbuehler, Konrad ETH Zürich, Institute for Chemical and Bioengineering, Zürich, Switzerland
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    27.06.2015
Published in:
  • Particle and Fibre Toxicology. - 2015, vol. 12, no. 1, p. 18
3R
A549
Air liquid interface
ALICE
Inhalation exposure
MLE 12
MLE12
Epithelial cell monolayers
PBPK model
PBTK model
English The lung epithelial tissue barrier represents the main portal for entry of inhaled nanoparticles (NPs) into the systemic circulation. Thus great efforts are currently being made to determine adverse health effects associated with inhalation of NPs. However, to date very little is known about factors that determine the pulmonary translocation of NPs and their subsequent distribution to secondary organs.Methods: A novel two-step approach to assess the biokinetics of inhaled NPs is presented. In a first step, alveolar epithelial cellular monolayers (CMLs) at the air-liquid interface (ALI) were exposed to aerosolized NPs to determine their translocation kinetics across the epithelial tissue barrier. Then, in a second step, the distribution to secondary organs was predicted with a physiologically based pharmacokinetic (PBPK) model. Monodisperse, spherical, well-characterized, negatively charged gold nanoparticles (AuNP) were used as model NPs. Furthermore, to obtain a comprehensive picture of the translocation kinetics in different species, human (A549) and mouse (MLE-12) alveolar epithelial CMLs were exposed to ionic gold and to various doses (i.e., 25, 50, 100, 150, 200 ng/cm 2 ) and sizes (i.e., 2, 7, 18, 46, 80 nm) of AuNP, and incubated post-exposure for different time periods (i.e., 0, 2, 8, 24, 48, 72 h).Results: The translocation kinetics of the AuNP across A549 and MLE-12 CMLs was similar. The translocated fraction was (1) inversely proportional to the particle size, and (2) independent of the applied dose (up to 100 ng/cm 2 ). Furthermore, supplementing the A549 CML with two immune cells, i.e., macrophages and dendritic cells, did not significantly change the amount of translocated AuNP. Comparison of the measured translocation kinetics and modeled biodistribution with in vivo data from literature showed that the combination of in vitro and in silico methods can accurately predict the in vivo biokinetics of inhaled/instilled AuNP.Conclusion: Our approach to combine in vitro and in silico methods for assessing the pulmonary translocation and biodistribution of NPs has the potential to replace short-term animal studies which aim to assess the pulmonary absorption and biodistribution of NPs, and to serve as a screening tool to identify NPs of special concern.
Faculty
Faculté des sciences et de médecine
Department
Département de Chimie
Language
  • English
Classification
Chemistry
License
License undefined
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Persistent URL
https://folia.unifr.ch/unifr/documents/304356
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