Development and validation of a dynamic drug screening platform for ADME testing .
Development and validation of a dynamic drug screening platform for ADME testing .
批准号:
131725
负责人:
金额:
$22.01万
依托单位:
依托单位国家:
英国
项目类别:
Feasibility Studies
财政年份:
2014
资助国家:
英国
项目状态:
已结题
起止时间:
2014 至 --
中文摘要
Caco-2细胞系是通过模拟小肠来预测药物体外吸收和渗透性的金标准。然而,这个模型缺乏代表小肠的生理功能之一的动态运动(蠕动)。在我们的研究中,我们通过使用MICA技术创建动态的体外环境来研究静态Caco-2细胞模型与动态肠道模型之间的相似性。到目前为止,我们的结果已经表明,MICA的技术改善了所选药物的吸收,它们的渗透性与人类肠道中发现的更相似。我们的数据表明,将MICA技术应用于Caco-2药物渗透性测定,可以通过体外试验更好地预测体内药物吸收速率。这项可行性研究将使我们能够严格对照黄金标准进行测试,并为药品市场产生一种新的检测方法。我们的研究最终将减少动物研究,并通过管道将更多的药物应用于医疗保健。
英文摘要
The Caco-2 cell line is the gold standard for the prediction of drug absorption and permeability in vitro by mimicking the small intestine. However, this model lacks the dynamic motion which represents one of the physiological functions of the small intestine (peristalsis). In our research, we investigate the possibility the similarity between the static Caco-2 cell model and the dynamic intestine by creating a dynamic in vitro environment using MICA technology. Our results to date have shown that MICA’ technology improves the absorption of the selected drugs, and their permeability is more similar to that found in the human intestine. Our data suggests that MICA’ technology applied to Caco-2 drug permeability assay could be used to a better predict, using in vitro assays, the in vivo human drug absorption rates. This feasibility study will enable us to test rigorously against the gold standards and generate a new assay for the pharmaceutical market. Our research will lead ultimately to a reduction in animal research and more drugs coming through the pipeline to applications in healthcare.
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