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 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.
State Key Laboratory of Fine Chemicals, Department of Chemical Engineering, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.|School of Pharmaceutical Science and Technology, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.
Fan
F
An
State Key Laboratory of Fine Chemicals, Department of Chemical Engineering, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.|School of Pharmaceutical Science and Technology, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.
Yueyang
Y
Qu
State Key Laboratory of Fine Chemicals, Department of Chemical Engineering, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.|School of Pharmaceutical Science and Technology, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.
Yong
Y
Luo
Department of Chemistry, Georgia State University, Atlanta, GA, 30302, USA.
Ning
N
Fang
State Key Laboratory of Fine Chemicals, Department of Chemical Engineering, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.|School of Pharmaceutical Science and Technology, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.
Yang
Y
Liu
State Key Laboratory of Fine Chemicals, Department of Chemical Engineering, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.|School of Pharmaceutical Science and Technology, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.
Zhigang
Z
Gao
State Key Laboratory of Fine Chemicals, Department of Chemical Engineering, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.|School of Pharmaceutical Science and Technology, Dalian University of Technology, 2 Linggong Rd., Dalian 116024, China.
Weijie
W
Zhao
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Bingcheng
B
Lin
D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D056656:Lab-On-A-Chip Devices