Development and validation of a dynamic drug screening platform for ADME testing

用于 ADME 测试的动态药物筛选平台的开发和验证

• 批准号: EP/M506862/1
• 负责人: Neil Telling
• 金额: $ 5.86万
• 依托单位: Keele University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FM506862%2F1
• 关键词: Development; validation; dynamic; drug; screening

The Caco-2 cell line is the gold standard for the prediction of drug absorption and permeability in vitro by mimicking thesmall intestine. However, this model lacks the dynamic motion which represents one of the physiological functions of thesmall intestine (peristalsis). In our research, we investigate the possible similarity between the static Caco-2 cell model andthe dynamic intestine by creating a dynamic in vitro environment using MICA technology. In order to obtain the dynamiccells environment, MICA Biosystems' technology was applied to the Caco-2 cell line. With this technology it is possible tointeract, by the application of an external magnetic field, with the magnetic core nanoparticles specifically attached on thecells membrane, and produce deformations on the membrane which mimic a dynamic cell in vivo environment e.g. in thecase of the gut similar to peristaltic contractions. Our results to date have shown that MICA' technology improves theabsorption of the selected drugs, and their permeability is more similar to that found in the human intestine. Our datasuggests that MICA' technology applied to Caco-2 drug permeability assay could be used to better predict, using in vitroassays, the in vivo human drug absorption rates. This feasibility study will enable us to test rigorously against the goldstandards and generate a new assay for the pharmaceutical market.

Caco-2细胞系是通过模拟小肠预测药物体外吸收和渗透性的金标准。然而，该模型缺乏代表小肠生理功能之一的动态运动。在我们的研究中，我们通过使用MICA技术创建动态体外环境来研究静态Caco-2细胞模型和动态肠道之间可能的相似性。为了获得动态的细胞环境，将MICA Biosystems的技术应用于Caco-2细胞系。利用这种技术，通过施加外部磁场，可以与特异性附着在细胞膜上的磁性核心纳米颗粒相互作用，并在膜上产生变形，其模拟动态细胞体内环境，例如在肠道中类似于蠕动收缩。迄今为止，我们的研究结果表明，MICA技术改善了所选药物的吸收，其渗透性与人体肠道中的渗透性更相似。我们的研究表明，MICA技术应用于Caco-2药物渗透性测定，可以用于更好地预测，使用在体外测定，在体内人体药物吸收率。这项可行性研究将使我们能够严格按照黄金标准进行测试，并为制药市场提供新的检测方法。