Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice

Wei-Yu Chen,1 Yi-Hsien Cheng,2 Nan-Hung Hsieh,3 Bo-Chun Wu,2 Wei-Chun Chou,4 Chia-Chi Ho,4 Jen-Kun Chen,5 Chung-Min Liao,2,* Pinpin Lin4,* 1Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 2Department of Bioenvironmental Systems Engineering, Natio...

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Autores principales:	Chen WY, Cheng YH, Hsieh NH, Wu BC, Chou WC, Ho CC, Chen JK, Liao CM, Lin P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8994e5d4d9144a88a92fdf41ec5a4d7f
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spelling	oai:doaj.org-article:8994e5d4d9144a88a92fdf41ec5a4d7f2021-12-02T05:40:44ZPhysiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice1178-2013https://doaj.org/article/8994e5d4d9144a88a92fdf41ec5a4d7f2015-10-01T00:00:00Zhttps://www.dovepress.com/physiologically-based-pharmacokinetic-modeling-of-zinc-oxide-nanoparti-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wei-Yu Chen,1 Yi-Hsien Cheng,2 Nan-Hung Hsieh,3 Bo-Chun Wu,2 Wei-Chun Chou,4 Chia-Chi Ho,4 Jen-Kun Chen,5 Chung-Min Liao,2,* Pinpin Lin4,* 1Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 2Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 3Institute of Labor, Occupational Safety and Health, Ministry of Labor, New Taipei City, 4National Institute of Environmental Health Sciences, 5Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Taiwan *These authors contributed equally to this work Abstract: Zinc oxide nanoparticles (ZnO NPs) have been widely used in consumer products, therapeutic agents, and drug delivery systems. However, the fate and behavior of ZnO NPs in living organisms are not well described. The purpose of this study was to develop a physiologically based pharmacokinetic model to describe the dynamic interactions of 65ZnO NPs in mice. We estimated key physicochemical parameters of partition coefficients and excretion or elimination rates, based on our previously published data quantifying the biodistributions of 10 nm and 71 nm 65ZnO NPs and zinc nitrate (65Zn(NO3)2) in various mice tissues. The time-dependent partition coefficients and excretion or elimination rates were used to construct our physiologically based pharmacokinetic model. In general, tissue partition coefficients of 65ZnO NPs were greater than those of 65Zn(NO3)2, particularly the lung partition coefficient of 10 nm 65ZnO NPs. Sensitivity analysis revealed that 71 nm 65ZnO NPs and 65Zn(NO3)2 were sensitive to excretion and elimination rates in the liver and gastrointestinal tract. Although the partition coefficient of the brain was relative low, it increased time-dependently for 65ZnO NPs and 65Zn(NO3)2. The simulation of 65Zn(NO3)2 was well fitted with the experimental data. However, replacing partition coefficients of 65ZnO NPs with those of 65Zn(NO3)2 after day 7 greatly improved the fitness of simulation, suggesting that ZnO NPs might decompose to zinc ion after day 7. In this study, we successfully established a potentially predictive dynamic model for slowly decomposed NPs. More caution is suggested for exposure to 65ZnO NPs <10 nm because those small 65ZnO NPs tend to accumulate in the body for a relatively longer time than 71 nm 65ZnO NPs and 65Zn(NO3)2 do. Keywords: zinc nanomaterials, bioaccumulation, biodistribution, PBPK modeling, partition coefficientChen WYCheng YHHsieh NHWu BCChou WCHo CCChen JKLiao CMLin PDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6277-6292 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen WY Cheng YH Hsieh NH Wu BC Chou WC Ho CC Chen JK Liao CM Lin P Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice
description	Wei-Yu Chen,1 Yi-Hsien Cheng,2 Nan-Hung Hsieh,3 Bo-Chun Wu,2 Wei-Chun Chou,4 Chia-Chi Ho,4 Jen-Kun Chen,5 Chung-Min Liao,2,* Pinpin Lin4,* 1Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 2Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 3Institute of Labor, Occupational Safety and Health, Ministry of Labor, New Taipei City, 4National Institute of Environmental Health Sciences, 5Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Taiwan *These authors contributed equally to this work Abstract: Zinc oxide nanoparticles (ZnO NPs) have been widely used in consumer products, therapeutic agents, and drug delivery systems. However, the fate and behavior of ZnO NPs in living organisms are not well described. The purpose of this study was to develop a physiologically based pharmacokinetic model to describe the dynamic interactions of 65ZnO NPs in mice. We estimated key physicochemical parameters of partition coefficients and excretion or elimination rates, based on our previously published data quantifying the biodistributions of 10 nm and 71 nm 65ZnO NPs and zinc nitrate (65Zn(NO3)2) in various mice tissues. The time-dependent partition coefficients and excretion or elimination rates were used to construct our physiologically based pharmacokinetic model. In general, tissue partition coefficients of 65ZnO NPs were greater than those of 65Zn(NO3)2, particularly the lung partition coefficient of 10 nm 65ZnO NPs. Sensitivity analysis revealed that 71 nm 65ZnO NPs and 65Zn(NO3)2 were sensitive to excretion and elimination rates in the liver and gastrointestinal tract. Although the partition coefficient of the brain was relative low, it increased time-dependently for 65ZnO NPs and 65Zn(NO3)2. The simulation of 65Zn(NO3)2 was well fitted with the experimental data. However, replacing partition coefficients of 65ZnO NPs with those of 65Zn(NO3)2 after day 7 greatly improved the fitness of simulation, suggesting that ZnO NPs might decompose to zinc ion after day 7. In this study, we successfully established a potentially predictive dynamic model for slowly decomposed NPs. More caution is suggested for exposure to 65ZnO NPs <10 nm because those small 65ZnO NPs tend to accumulate in the body for a relatively longer time than 71 nm 65ZnO NPs and 65Zn(NO3)2 do. Keywords: zinc nanomaterials, bioaccumulation, biodistribution, PBPK modeling, partition coefficient
format	article
author	Chen WY Cheng YH Hsieh NH Wu BC Chou WC Ho CC Chen JK Liao CM Lin P
author_facet	Chen WY Cheng YH Hsieh NH Wu BC Chou WC Ho CC Chen JK Liao CM Lin P
author_sort	Chen WY
title	Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice
title_short	Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice
title_full	Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice
title_fullStr	Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice
title_full_unstemmed	Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice
title_sort	physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/8994e5d4d9144a88a92fdf41ec5a4d7f
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Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice

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