Published February 1, 2022 | Version v1
Journal article Open

Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro—In Vivo Correlation

  • 1. 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; alena.manova@stuba.sk (A.M.); peter.simon@stuba.sk (P.S.); Correspondence: tibor.dubaj@stuba.sk
  • 2. Cancer Research Institute, Biomedical Research Center SAS, v.v.i., Dubravska cesta 9, 845 05 Bratislava, Slovakia; Katarina.Kozics@savba.sk (K.K.); monika.sramkova@savba.sk (M.S.); alena.gabelova@savba.sk (A.G.)
  • 3. 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; alena.manova@stuba.sk (A.M.); peter.simon@stuba.sk (P.S.)
  • 4. Campus UAB, Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Bellaterra, 08193 Barcelona, Spain; neus.bastus@icn2.cat (N.G.B.); oscarhernando.moriones@icn2.cat (O.H.M.); victor.puntes@icn2.cat (V.P.)
  • 5. Fraunhofer Institute for Biomedical Engineering IBMT, 66280 Sulzbach, Germany; yvonne.kohl@ibmt.fraunhofer.de
  • 6. Health Effects Laboratory, NILU-Norwegian Institute for Air Research, 2007 Kjeller, Norway; mdu@nilu.no (M.D.); erp@nilu.no (E.R.-P.)
  • 7. Campus UAB, Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Bellaterra, 08193 Barcelona, Spain; neus.bastus@icn2.cat (N.G.B.); oscarhernando.moriones@icn2.cat (O.H.M.); victor.puntes@icn2.cat (V.P.); Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain; Vall d'Hebron Institut de Recerca (VHIR), 08032 Barcelona, Spain
  • 8. School of Chemistry, University of Leeds, Leeds LS2 9JT, UK; A.L.Nelson@leeds.ac.uk

Description

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.

Notes

This research was funded by the European Commission under the Horizon 2020 programme (HISENTS, Grant Agreement No. 685817 and VISION, Grant Agreement No. 857381). Financial support from the Structural Funds of EU by implementation of the project "Strategic research in SMART monitoring, treatment, and prevention against coronavirus (SARS-CoV-2)", ITMS 2014+ code NFP313011ASS8 co-financed by the European Regional Development Fund.

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Funding

VISION – Strategies to strengthen scientific excellence and innoVation capacIty for early diagnoSIs of gastrOintestinal caNcers 857381
European Commission