Intestinal Permeability of Drugs in Caco-2 Cells Cultured in Microfluidic Devices

Microfluidic devices are attracting attention for their ability to provide a biomimetic microenvironment wherein cells are arranged in a particular pattern and provided fluidic and mechanical forces. In this study, we evaluated drug transport across Caco-2 cell layers in microfluidic devices and inv...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2022/09/01, Vol.45(9), pp.1246-1253
Main Authors: Sasaki, Yuko, Tatsuoka, Hirotaka, Tsuda, Masahiro, Sumi, Takumi, Eguchi, Yuka, So, Kanako, Higuchi, Yuriko, Takayama, Kazuo, Torisawa, Yusuke, Yamashita, Fumiyoshi
Format: Article
Language:English
Subjects:
Caco-2
drug absorption
Drug metabolism
Fluid flow
Gene expression
Glycoproteins
gut-on-a-chip
Metabolism
Microenvironments
microfluidic device
Microfluidics
organ-on-a-chip
P-Glycoprotein
Permeability
Polydimethylsiloxane
Polyethylene
Polyethylene terephthalate
Rhodamine
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Summary:Microfluidic devices are attracting attention for their ability to provide a biomimetic microenvironment wherein cells are arranged in a particular pattern and provided fluidic and mechanical forces. In this study, we evaluated drug transport across Caco-2 cell layers in microfluidic devices and investigated the effects of fluid flow on drug transport and metabolism. We designed a microfluidic device that comprises two blocks of polydimethylsiloxane and a sandwiched polyethylene terephthalate membrane with pores 3.0 µm in diameter. When cultured in a dynamic fluid environment, Caco-2 cells were multilayered and developed microvilli on the surface as compared with a static environment. Drugs with higher lipophilicity exhibited higher permeability across the Caco-2 layers, as well as in the conventional method using Transwells, and the fluidic conditions had little effect on permeability. In the Caco-2 cell layers cultured in Transwells and microfluidic devices, the basal-to-apical transport of rhodamine 123, a substrate of P-glycoprotein, was greater than the apical-to-basal transport, and the presence of tariquidar, an inhibitor of P-glycoprotein, completely diminished asymmetric transport. Furthermore, fluidic conditions promoted the metabolism of temocapril by carboxylesterases. On the other hand, we showed that fluidic conditions have little effect on gene expression of several transporters and metabolic enzymes. These results provide useful information regarding the application of microfluidic devices in drug transport and metabolism studies.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b22-00092