Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro—In Vivo Correlation
Tibor Dubaj,
Katarina Kozics,
Monika Sramkova,
Alena Manova,
Neus G. Bastús,
Oscar H. Moriones,
Yvonne Kohl,
Maria Dusinska,
Elise Runden-Pran,
Victor Puntes,
Andrew Nelson,
Alena Gabelova,
Peter Simon
Affiliations
Tibor Dubaj
Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinskeho 9, 812 37 Bratislava, Slovakia
Katarina Kozics
Cancer Research Institute, Biomedical Research Center SAS, v.v.i., Dubravska cesta 9, 845 05 Bratislava, Slovakia
Monika Sramkova
Cancer Research Institute, Biomedical Research Center SAS, v.v.i., Dubravska cesta 9, 845 05 Bratislava, Slovakia
Alena Manova
Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinskeho 9, 812 37 Bratislava, Slovakia
Neus G. Bastús
Campus UAB, Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Bellaterra, 08193 Barcelona, Spain
Oscar H. Moriones
Campus UAB, Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Bellaterra, 08193 Barcelona, Spain
Yvonne Kohl
Fraunhofer Institute for Biomedical Engineering IBMT, 66280 Sulzbach, Germany
Maria Dusinska
Health Effects Laboratory, NILU-Norwegian Institute for Air Research, 2007 Kjeller, Norway
Elise Runden-Pran
Health Effects Laboratory, NILU-Norwegian Institute for Air Research, 2007 Kjeller, Norway
Victor Puntes
Campus UAB, Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Bellaterra, 08193 Barcelona, Spain
Andrew Nelson
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK
Alena Gabelova
Cancer Research Institute, Biomedical Research Center SAS, v.v.i., Dubravska cesta 9, 845 05 Bratislava, Slovakia
Peter Simon
Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinskeho 9, 812 37 Bratislava, Slovakia
Data suitable for assembling a physiologically-based pharmacokinetic (PBPK) model for nanoparticles (NPs) remain relatively scarce. Therefore, there is a trend in extrapolating the results of in vitro and in silico studies to in vivo nanoparticle hazard and risk assessment. To evaluate the reliability of such approach, a pharmacokinetic study was performed using the same polyethylene glycol-coated gold nanoparticles (PEG-AuNPs) in vitro and in vivo. As in vitro models, human cell lines TH1, A549, Hep G2, and 16HBE were employed. The in vivo PEG-AuNP biodistribution was assessed in rats. The internalization and exclusion of PEG-AuNPs in vitro were modeled as first-order rate processes with the partition coefficient describing the equilibrium distribution. The pharmacokinetic parameters were obtained by fitting the model to the in vitro data and subsequently used for PBPK simulation in vivo. Notable differences were observed in the internalized amount of Au in individual cell lines compared to the corresponding tissues in vivo, with the highest found for renal TH1 cells and kidneys. The main reason for these discrepancies is the absence of natural barriers in the in vitro conditions. Therefore, caution should be exercised when extrapolating in vitro data to predict the in vivo NP burden and response to exposure.
