Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles

Ulrika Carlander,1 Dingsheng Li,2 Olivier Jolliet,2 Claude Emond,3,4 Gunnar Johanson1 1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 3BioSimulation Con...

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Autores principales:	Carlander U, Li D, Jolliet O, Emond C, Johanson G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	nanoparticles physiologically based pharmacokinetic modeling PBPK pharmacokinetics intravenous administration phagocytosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6bb7ab44c7b140ed82c0f8feccbb7593
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spelling	oai:doaj.org-article:6bb7ab44c7b140ed82c0f8feccbb75932021-12-02T05:06:48ZToward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles1178-2013https://doaj.org/article/6bb7ab44c7b140ed82c0f8feccbb75932016-02-01T00:00:00Zhttps://www.dovepress.com/toward-a-general-physiologically-based-pharmacokinetic-model-for-intra-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ulrika Carlander,1 Dingsheng Li,2 Olivier Jolliet,2 Claude Emond,3,4 Gunnar Johanson1 1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 3BioSimulation Consulting Inc., Newark, DE, USA; 4Department of Environmental and Occupational Health, School of Public Health, University of Montreal, QC, Canada Abstract: To assess the potential toxicity of nanoparticles (NPs), information concerning their uptake and disposition (biokinetics) is essential. Experience with industrial chemicals and pharmaceutical drugs reveals that biokinetics can be described and predicted accurately by physiologically-based pharmacokinetic (PBPK) modeling. The nano PBPK models developed to date all concern a single type of NP. Our aim here was to extend a recent model for pegylated polyacrylamide NP in order to develop a more general PBPK model for nondegradable NPs injected intravenously into rats. The same model and physiological parameters were applied to pegylated polyacrylamide, uncoated polyacrylamide, gold, and titanium dioxide NPs, whereas NP-specific parameters were chosen on the basis of the best fit to the experimental time-courses of NP accumulation in various tissues. Our model describes the biokinetic behavior of all four types of NPs adequately, despite extensive differences in this behavior as well as in their physicochemical properties. In addition, this simulation demonstrated that the dose exerts a profound impact on the biokinetics, since saturation of the phagocytic cells at higher doses becomes a major limiting step. The fitted model parameters that were most dependent on NP type included the blood:tissue coefficients of permeability and the rate constant for phagocytic uptake. Since only four types of NPs with several differences in characteristics (dose, size, charge, shape, and surface properties) were used, the relationship between these characteristics and the NP-dependent model parameters could not be elucidated and more experimental data are required in this context. In this connection, intravenous biodistribution studies with associated PBPK analyses would provide the most insight. Keywords: nondegradable, PBPK, intravenous administration, phagocytosis, rats, nanorods, gold, titanium dioxide, polyacrylamide, polyethylene glycol coatingCarlander ULi DJolliet OEmond CJohanson GDove Medical Pressarticlenanoparticlesphysiologically based pharmacokinetic modelingPBPKpharmacokineticsintravenous administrationphagocytosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss Issue 1, Pp 625-640 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoparticles physiologically based pharmacokinetic modeling PBPK pharmacokinetics intravenous administration phagocytosis Medicine (General) R5-920
spellingShingle	nanoparticles physiologically based pharmacokinetic modeling PBPK pharmacokinetics intravenous administration phagocytosis Medicine (General) R5-920 Carlander U Li D Jolliet O Emond C Johanson G Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles
description	Ulrika Carlander,1 Dingsheng Li,2 Olivier Jolliet,2 Claude Emond,3,4 Gunnar Johanson1 1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 3BioSimulation Consulting Inc., Newark, DE, USA; 4Department of Environmental and Occupational Health, School of Public Health, University of Montreal, QC, Canada Abstract: To assess the potential toxicity of nanoparticles (NPs), information concerning their uptake and disposition (biokinetics) is essential. Experience with industrial chemicals and pharmaceutical drugs reveals that biokinetics can be described and predicted accurately by physiologically-based pharmacokinetic (PBPK) modeling. The nano PBPK models developed to date all concern a single type of NP. Our aim here was to extend a recent model for pegylated polyacrylamide NP in order to develop a more general PBPK model for nondegradable NPs injected intravenously into rats. The same model and physiological parameters were applied to pegylated polyacrylamide, uncoated polyacrylamide, gold, and titanium dioxide NPs, whereas NP-specific parameters were chosen on the basis of the best fit to the experimental time-courses of NP accumulation in various tissues. Our model describes the biokinetic behavior of all four types of NPs adequately, despite extensive differences in this behavior as well as in their physicochemical properties. In addition, this simulation demonstrated that the dose exerts a profound impact on the biokinetics, since saturation of the phagocytic cells at higher doses becomes a major limiting step. The fitted model parameters that were most dependent on NP type included the blood:tissue coefficients of permeability and the rate constant for phagocytic uptake. Since only four types of NPs with several differences in characteristics (dose, size, charge, shape, and surface properties) were used, the relationship between these characteristics and the NP-dependent model parameters could not be elucidated and more experimental data are required in this context. In this connection, intravenous biodistribution studies with associated PBPK analyses would provide the most insight. Keywords: nondegradable, PBPK, intravenous administration, phagocytosis, rats, nanorods, gold, titanium dioxide, polyacrylamide, polyethylene glycol coating
format	article
author	Carlander U Li D Jolliet O Emond C Johanson G
author_facet	Carlander U Li D Jolliet O Emond C Johanson G
author_sort	Carlander U
title	Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles
title_short	Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles
title_full	Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles
title_fullStr	Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles
title_full_unstemmed	Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles
title_sort	toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/6bb7ab44c7b140ed82c0f8feccbb7593
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Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles

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