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Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System

The pharmacokinetic (PK) properties of drug, which include drug absorption and excretion, play an important role in determining the in vivo pharmaceutical activity. However, current in vitro systems that model PK profiles are often limited by the in vivo-like concentration profile of a drug. Herein,...

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Autores principales: Guo, Yaqiong, Deng, Pengwei, Chen, Wenwen, Li, Zhongyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344513/
https://www.ncbi.nlm.nih.gov/pubmed/32486116
http://dx.doi.org/10.3390/mi11060551
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author Guo, Yaqiong
Deng, Pengwei
Chen, Wenwen
Li, Zhongyu
author_facet Guo, Yaqiong
Deng, Pengwei
Chen, Wenwen
Li, Zhongyu
author_sort Guo, Yaqiong
collection PubMed
description The pharmacokinetic (PK) properties of drug, which include drug absorption and excretion, play an important role in determining the in vivo pharmaceutical activity. However, current in vitro systems that model PK profiles are often limited by the in vivo-like concentration profile of a drug. Herein, we present a perfused and multi-layered microfluidic chip system to model the PK profile of anti-cancer drug 5-FU in vitro. The chip device contains two layers of culture channels sandwiched by a porous membrane, which allows for drug exposure and diffusion between the two channels. The integration of upper intestine cells (Caco-2) and bottom targeted cells within the device enables the generation of loading and clearance portions of a PK curve under peristaltic flow. Fluorescein as a test molecule was initially used to generate a concentration-time curve, investigating the effects of parameters of flow rate, administration time, and initial concentration on dynamic drug concentration profiles. Furthermore, anti-cancer drug 5-FU was performed to assess its pharmaceutical activity on target cells (human lung adenocarcinoma cells or human pulmonary alveolar epithelial cells) using different drug administration regimens. A dynamic, in vivo-like 5-FU exposure refers to PK profile regimen, led to generate a lower drug concentration (dynamically fluctuate from 0 to 1 μg/mL affected by absorption) compared to the constant exposure. Moreover, the PK profile regimen alleviates the drug-induced cytotoxicity on target cells. These results demonstrate the feasibility of determining the PK profiles using this microfluidic system with in vivo-like drug administration regimens. This established system may provide a powerful platform for the prediction of drug safety and effectiveness in the pharmaceutical research.
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spelling pubmed-73445132020-07-14 Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System Guo, Yaqiong Deng, Pengwei Chen, Wenwen Li, Zhongyu Micromachines (Basel) Article The pharmacokinetic (PK) properties of drug, which include drug absorption and excretion, play an important role in determining the in vivo pharmaceutical activity. However, current in vitro systems that model PK profiles are often limited by the in vivo-like concentration profile of a drug. Herein, we present a perfused and multi-layered microfluidic chip system to model the PK profile of anti-cancer drug 5-FU in vitro. The chip device contains two layers of culture channels sandwiched by a porous membrane, which allows for drug exposure and diffusion between the two channels. The integration of upper intestine cells (Caco-2) and bottom targeted cells within the device enables the generation of loading and clearance portions of a PK curve under peristaltic flow. Fluorescein as a test molecule was initially used to generate a concentration-time curve, investigating the effects of parameters of flow rate, administration time, and initial concentration on dynamic drug concentration profiles. Furthermore, anti-cancer drug 5-FU was performed to assess its pharmaceutical activity on target cells (human lung adenocarcinoma cells or human pulmonary alveolar epithelial cells) using different drug administration regimens. A dynamic, in vivo-like 5-FU exposure refers to PK profile regimen, led to generate a lower drug concentration (dynamically fluctuate from 0 to 1 μg/mL affected by absorption) compared to the constant exposure. Moreover, the PK profile regimen alleviates the drug-induced cytotoxicity on target cells. These results demonstrate the feasibility of determining the PK profiles using this microfluidic system with in vivo-like drug administration regimens. This established system may provide a powerful platform for the prediction of drug safety and effectiveness in the pharmaceutical research. MDPI 2020-05-29 /pmc/articles/PMC7344513/ /pubmed/32486116 http://dx.doi.org/10.3390/mi11060551 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guo, Yaqiong
Deng, Pengwei
Chen, Wenwen
Li, Zhongyu
Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System
title Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System
title_full Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System
title_fullStr Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System
title_full_unstemmed Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System
title_short Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System
title_sort modeling pharmacokinetic profiles for assessment of anti-cancer drug on a microfluidic system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344513/
https://www.ncbi.nlm.nih.gov/pubmed/32486116
http://dx.doi.org/10.3390/mi11060551
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