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

被引:31
作者
Dubaj, Tibor [1 ]
Kozics, Katarina [2 ]
Sramkova, Monika [2 ]
Manova, Alena [1 ]
Bastus, Neus G. [3 ,4 ]
Moriones, Oscar H. [3 ,4 ]
Kohl, Yvonne [5 ]
Dusinska, Maria [6 ]
Runden-Pran, Elise [6 ]
Puntes, Victor [3 ,4 ,7 ,8 ]
Nelson, Andrew [9 ]
Gabelova, Alena [2 ]
Simon, Peter [1 ]
机构
[1] Slovak Univ Technol Bratislava, Fac Chem & Food Technol, Inst Phys Chem & Chem Phys, Radlinskeho 9, Bratislava 81237, Slovakia
[2] Biomed Res Ctr SAS, Vvi, Canc Res Inst, Dubravska Cesta 9, Bratislava 84505, Slovakia
[3] CSIC, Catalan Inst Nanosci & Nanotechnol ICN2, Campus UAB, Barcelona 08193, Spain
[4] BIST, Barcelona 08193, Spain
[5] Fraunhofer Inst Biomed Engn IBMT, D-66280 Sulzbach, Germany
[6] NILU Norwegian Inst Air Res, Hlth Effects Lab, N-2007 Kjeller, Norway
[7] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona 08010, Spain
[8] Vall dHebron Inst Recerca VHIR, Barcelona 08032, Spain
[9] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England
关键词
gold nanoparticles; human cell lines; pharmacokinetics; PBPK model; IVIVE; RISK-ASSESSMENT; MODEL; TOXICITY; BARRIER; BIODISTRIBUTION; TRANSPORT;
D O I
10.3390/nano12030511
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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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页数:12
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