Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro-In Vivo Correlation.
Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro-In Vivo Correlation.
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DOI：
10.3390/nano12030511
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发表时间：
2022-02-01
期刊：
影响因子：
--
通讯作者：
Simon P
中科院分区：
文献类型：
--
作者：
Dubaj T;Kozics K;Sramkova M;Manova A;Bastús NG;Moriones OH;Kohl Y;Dusinska M;Runden-Pran E;Puntes V;Nelson A;Gabelova A;Simon P
适用于组装纳米颗粒（NP）的生理学药代动力学（PBPK）模型的数据仍然相对稀缺。因此，有一种趋势是将体外和计算机模拟研究的结果外推至体内纳米颗粒危害和风险评估。为了评估这种方法的可靠性，使用相同的聚乙二醇包覆的金纳米颗粒（PEG-AuNPs）在体外和体内进行药代动力学研究。作为体外模型，使用人细胞系TH 1、A549、Hep G2和16 HBE。在大鼠中评估体内PEG-AuNP生物分布。PEG-AuNPs在体外的内化和排阻被建模为一级速率过程，分配系数描述平衡分布。通过将模型拟合到体外数据获得药代动力学参数，随后用于体内PBPK模拟。与体内相应组织相比，在单个细胞系中观察到Au的内化量的显著差异，其中在肾TH 1细胞和肾中发现最高。这些差异的主要原因是在体外条件下缺乏天然屏障。因此，外推体外数据以预测体内NP负荷和暴露反应时应谨慎。
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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DOI：
10.3390/nano11071702
发表时间：
2021-06-28
期刊：
Nanomaterials (Basel, Switzerland)
影响因子：
--
作者：
Kozics K;Sramkova M;Kopecka K;Begerova P;Manova A;Krivosikova Z;Sevcikova Z;Liskova A;Rollerova E;Dubaj T;Puntes V;Wsolova L;Simon P;Tulinska J;Gabelova A
通讯作者：
Gabelova A
影响因子：
17.4
作者：
Gustafson HH;Holt-Casper D;Grainger DW;Ghandehari H
通讯作者：
Ghandehari H
影响因子：
5
作者：
Bachler, Gerald;von Goetz, Natalie;Hungerbuhler, Konrad
通讯作者：
Hungerbuhler, Konrad
影响因子：
3
作者：
Dohle, Eva;Singh, Smriti;Kirkpatrick, C. James
通讯作者：
Kirkpatrick, C. James
影响因子：
4
作者：
Callaghan PJ;Ferrick B;Rybakovsky E;Thomas S;Mullin JM
通讯作者：
Mullin JM