60dcd2235fafe89317f94ab4d602fc80 pmc_35159859.pdf f2dd5c82a4f79f68824c79ee56969d3a01378c6f pmc_35159859.pdf 7b5a1bb6c70d10158c0d6e8da501c5443e8763082061e6120ae66424aea67592 pmc_35159859.pdf Title: Pharmacokinetics of PEGylated Gold Nanoparticles:In Vitro—In Vivo Correlation Subject: 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. Keywords: gold nanoparticles; human cell lines; pharmacokinetics; PBPK model; IVIVE Author: 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 and Peter Simon Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 1 13:53:50 2022 CET ModDate: Tue Feb 1 15:09:53 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1203170 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GMZEJB+VnURWPalladioL Type 1 Custom yes yes no 10 0 BMFVQH+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 ZPVCED+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 XTUJAV+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 ENLEMO+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 NPLVPL+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 56 0 WTPQBM+CMSY10 Type 1 Builtin yes yes no 81 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 85 0 SOSTRQ+CMR10 Type 1 Builtin yes yes no 95 0 FIDYHR+URWPalladioL-BoldItal Type 1 Custom yes yes no 99 0 RMRVLO+MSAM10 Type 1 Builtin yes yes no 103 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 115 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 119 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 123 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 127 0 ArialMT TrueType WinAnsi no no no 134 0 Arial-BoldMT TrueType WinAnsi no no no 137 0 ZPGVCH+CMEX10 Type 1 Builtin yes yes no 180 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 188 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 192 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 196 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 200 0 ArialMT TrueType WinAnsi no no no 209 0 SymbolMT CID TrueType Identity-H yes no yes 213 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 232 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 236 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 240 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 244 0 SymbolMT CID TrueType Identity-H yes no yes 252 0 ArialMT TrueType WinAnsi no no no 264 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-04-01 02:22:29 CEST RepresentationInformation: pmc_35159859.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-02-27 18:43:42 CET Size: 1203170 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 433 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Gold Nanoparticles Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Cell Lines Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Cell Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Biodistribution and Accumulation of PEG-AuNPs In Vivo Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Quantification of PEG-AuNPs in the Cells, Blood, and Organs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Data Treatment and Statistics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Results and Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: In Vitro Pharmacokinetic Study Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Kinetic Analysis of Experiments with Cell Cultures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: In Vivo Pharmacokinetic Study Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Transfer of Parameters from In Vitro to In Vivo Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: Pharmacokinetics of PEGylated Gold Nanoparticles:In Vitro In Vivo Correlation Author: 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 and Peter Simon Subject: 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. 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