Department of Applied Biological Chemistry, School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.
Anal Chem. 2010 Dec 15;82(24):9983-8. doi: 10.1021/ac100806x. Epub 2010 Nov 23.
Oral medicines and food constituents are absorbed in the intestine and metabolized in the liver, after which they exhibit their activity toward a target tissue. Micromodels of human tissues were developed to mimic these processes and bioactivities. By integrating the micromodels, we realized a micro total bioassay system for oral substances; this system comprised a microintestine, microliver, and the target components. The microchip was composed of a slide glass and polydimethylsiloxane (PDMS) sheets with microchannels fabricated by photolithography. Caco-2 cells were cultured in the intestine component, and HepG2 cells, in the liver component. The human breast carcinoma MCF-7 cells were cultured in the target component, and the activities of anticancer agents and estrogen-like substances were successfully assayed. By using this system, the overall properties of the ingested cyclophosphamide, epirubicin, 17-β estradiol, and soy isoflavone, i.e., their intestinal absorption, hepatic metabolism, and bioactivity toward target cells, could be assayed with operative ease. Further, the assay time and cell consumption were reduced compared to those in conventional in vitro bioassay systems.
口服药物和食物成分在肠道中被吸收，并在肝脏中代谢，然后在靶向组织中发挥其活性。为了模拟这些过程和生物活性，开发了人类组织的微模型。通过整合这些微模型，我们实现了一个用于口服物质的微全生物分析系统；该系统包括微肠道、微肝脏和靶成分。微芯片由载玻片和聚二甲基硅氧烷（PDMS）片组成，微通道通过光刻技术制造。Caco-2 细胞在肠道成分中培养，HepG2 细胞在肝脏成分中培养。人乳腺癌 MCF-7 细胞在靶成分中培养，并成功检测了抗癌剂和类雌激素物质的活性。通过使用该系统，可以轻松操作评估摄入的环磷酰胺、表柔比星、17-β 雌二醇和大豆异黄酮的整体性质，包括它们的肠道吸收、肝脏代谢和对靶细胞的生物活性。此外，与传统的体外生物分析系统相比，该方法缩短了检测时间并减少了细胞消耗。
