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:
EP/M506862/1
负责人:
Neil Telling
金额:
$5.86万
依托单位:
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
项目状态:
已结题
起止时间:
2014 至 --
中文摘要
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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 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.
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