期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 45, 期 9, 页码 1246-1253出版社
PHARMACEUTICAL SOC JAPAN
关键词
microfluidic device; polydimethylsiloxane; Caco-2; organ-on-a-chip; gut-on-a-chip; drug absorption
资金
- AMED [21be0304202h0005, 20be0304401h0204]
Microfluidic devices are a promising tool for studying drug transport and metabolism. This study investigated drug transport across Caco-2 cell layers in microfluidic devices and found that drug lipophilicity influenced permeability. Fluidic conditions also promoted drug metabolism. These findings provide valuable information for the application of microfluidic devices in drug research.
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 mu m 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 per-meability 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.
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