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A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process

New techniques are urgently needed to replace conventional long and costly pre-clinical testing in the new drug administration process. In this study, a laminated microfluidic device was fabricated to mimic the drug ADME response test in vivo. This proposed device was loaded and cultured with functi...

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Autores principales: An, Fan, Qu, Yueyang, Luo, Yong, Fang, Ning, Liu, Yang, Gao, Zhigang, Zhao, Weijie, Lin, Bingcheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848557/
https://www.ncbi.nlm.nih.gov/pubmed/27122192
http://dx.doi.org/10.1038/srep25022
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author An, Fan
Qu, Yueyang
Luo, Yong
Fang, Ning
Liu, Yang
Gao, Zhigang
Zhao, Weijie
Lin, Bingcheng
author_facet An, Fan
Qu, Yueyang
Luo, Yong
Fang, Ning
Liu, Yang
Gao, Zhigang
Zhao, Weijie
Lin, Bingcheng
author_sort An, Fan
collection PubMed
description New techniques are urgently needed to replace conventional long and costly pre-clinical testing in the new drug administration process. In this study, a laminated microfluidic device was fabricated to mimic the drug ADME response test in vivo. This proposed device was loaded and cultured with functional cells for drug response investigation and organ tissues that are involved in ADME testing. The drug was introduced from the top of the device and first absorbed by the Caco-2 cell layer, and then metabolized by the primary hepatocyte layer. It subsequently interacted with the MCF-7 cell layer, distributed in the lung, heart and fat tissues, and was finally eliminated through the dialysis membrane. Throughout this on-chip ADME process, the proposed device can be used as a reliable tool to simultaneously evaluate the drug anti-tumor activity, hepatotoxicity and pharmacokinetics. Furthermore, this device was proven to be able to reflect the hepatic metabolism of a drug, drug distribution in the target tissues, and the administration method of a drug. Furthermore, this microdevice is expected to reduce the number of drug candidates and accelerate the pre-clinical testing process subject to animal testing upon adaptation in new drug discovery.
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spelling pubmed-48485572016-05-05 A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process An, Fan Qu, Yueyang Luo, Yong Fang, Ning Liu, Yang Gao, Zhigang Zhao, Weijie Lin, Bingcheng Sci Rep Article New techniques are urgently needed to replace conventional long and costly pre-clinical testing in the new drug administration process. In this study, a laminated microfluidic device was fabricated to mimic the drug ADME response test in vivo. This proposed device was loaded and cultured with functional cells for drug response investigation and organ tissues that are involved in ADME testing. The drug was introduced from the top of the device and first absorbed by the Caco-2 cell layer, and then metabolized by the primary hepatocyte layer. It subsequently interacted with the MCF-7 cell layer, distributed in the lung, heart and fat tissues, and was finally eliminated through the dialysis membrane. Throughout this on-chip ADME process, the proposed device can be used as a reliable tool to simultaneously evaluate the drug anti-tumor activity, hepatotoxicity and pharmacokinetics. Furthermore, this device was proven to be able to reflect the hepatic metabolism of a drug, drug distribution in the target tissues, and the administration method of a drug. Furthermore, this microdevice is expected to reduce the number of drug candidates and accelerate the pre-clinical testing process subject to animal testing upon adaptation in new drug discovery. Nature Publishing Group 2016-04-28 /pmc/articles/PMC4848557/ /pubmed/27122192 http://dx.doi.org/10.1038/srep25022 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
An, Fan
Qu, Yueyang
Luo, Yong
Fang, Ning
Liu, Yang
Gao, Zhigang
Zhao, Weijie
Lin, Bingcheng
A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process
title A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process
title_full A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process
title_fullStr A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process
title_full_unstemmed A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process
title_short A Laminated Microfluidic Device for Comprehensive Preclinical Testing in the Drug ADME Process
title_sort laminated microfluidic device for comprehensive preclinical testing in the drug adme process
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848557/
https://www.ncbi.nlm.nih.gov/pubmed/27122192
http://dx.doi.org/10.1038/srep25022
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