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Issue 4, 2010
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A microfluidic device for a pharmacokinetic–pharmacodynamic (PKPD) model on a chip

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Abstract

Drug discovery is often impeded by the poor predictability of in vitro assays for drug toxicity. One primary reason for this observation is the inability to reproduce the pharmacokinetics (PK) of drugs in vitro. Mathematical models to predict the pharmacokinetics–pharmacodynamics (PKPD) of drugs are available, but have several limitations, preventing broader application. A microscale cell culture analog (µCCA) is a microfluidic device based on a PKPD model, where multiple cell culture chambers are connected with fluidic channels to mimic multi-organ interactions and test drug toxicity in a pharmacokinetic-based manner. One critical issue with microfluidics, including the µCCA, is that specialized techniques are required for assembly and operation, limiting its usability to non-experts. Here, we describe a novel design, with enhanced usability while allowing hydrogel-cell cultures of multiple types. Gravity-induced flow enables pumpless operation and prevents bubble formation. Three cell lines representing the liver, tumor and marrow were cultured in the three-chamber µCCA to test the toxicity of an anticancer drug, 5-fluorouracil. The result was analyzed with a PKPD model of the device, and compared with the result in static conditions. Each cell type exhibited differential responses to 5-FU, and the responses in the microfluidic environment were different from those in static environment. Combination of a mathematical modeling approach (PKPD modeling) and an in vitro experimental approach (µCCA) provides a novel platform with improved predictability for testing drug toxicity and can help researchers gain a better insight into the drug's mechanism of action.

Graphical abstract: A microfluidic device for a pharmacokinetic–pharmacodynamic (PK–PD) model on a chip

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Publication details

The article was received on 01 Sep 2009, accepted on 03 Dec 2009 and first published on 05 Jan 2010


Article type: Paper
DOI: 10.1039/B917763A
Citation: Lab Chip, 2010,10, 446-455
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    A microfluidic device for a pharmacokinetic–pharmacodynamic (PKPD) model on a chip

    J. H. Sung, C. Kam and M. L. Shuler, Lab Chip, 2010, 10, 446
    DOI: 10.1039/B917763A

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