Micro Total Bioassay System for Ingested Substances: Assessment of Intestinal Absorption, Hepatic Metabolism, and Bioactivity
Micro Total Bioassay System for Ingested Substances: Assessment of Intestinal Absorption, Hepatic Metabolism, and Bioactivity
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DOI：
10.1021/ac100806x
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发表时间：
2010-12-15
影响因子：
7.4
通讯作者：
Yoshimura, Etsuro
中科院分区：
文献类型：
--
作者：
Imura, Yuki;Sato, Kiichi;Yoshimura, Etsuro
口服药物和食物成分在肠道中吸收并在肝脏中代谢，之后它们对靶组织表现出活性。人类组织的微模型被开发来模拟这些过程和生物活性。通过整合微模型，我们实现了一个微型全生物测定系统的口服物质，该系统包括一个微肠，微肝，和目标成分。微芯片由载玻片和具有微通道的聚二甲基硅氧烷（PDMS）片组成，微通道通过光刻法制备。Caco-2细胞在肠组分中培养，HepG 2细胞在肝组分中培养。在目标组分中培养人乳腺癌MCF-7细胞，并成功地测定了抗癌剂和雌激素样物质的活性。通过使用该系统，摄入的环磷酰胺、表阿霉素、17-β雌二醇和大豆异黄酮的总体性质，即，它们的肠吸收、肝代谢和对靶细胞的生物活性可以容易地进行测定。此外，与常规体外生物测定系统相比，测定时间和细胞消耗减少。
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-beta estradiol, and soy isoflavone, i.e., their intestinal absorption, hepatic metalbolism, 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.