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In vitro models of the blood-brain barrier for the study of drug delivery to the brain

机译:血脑屏障的体外模型,用于研究向大脑的药物输送

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摘要

The most important obstacle to the drug delivery into the brain is the presence of the blood-brain barrier, which limits the traffic of substances between the blood and the nervous tissue. Therefore, adequate in vitro models need to be developed in order to characterize the penetration properties of drug candidates into the central nervous system. This review article summarizes the presently used and the most promising in vitro BBB models based on the culture of brain endothelial cells. Robust models can be obtained using primary porcine brain endothelial cells and rodent coculture models, which have low paracellular permeability and express functional efflux transporters, showing good correlation of drug penetration data with in vivo results. Models mimicking the in vivo anatomophysiological complexity of the BBB are also available, including triple coculture (culture of brain endothelial cells in the presence of pericytes and astrocytes), dynamic, and microfluidic models; however, these are not suitable for rapid, high throughput studies. Potent human cell lines would be needed for easily available and reproducible models which avoid interspecies differences.
机译:药物进入大脑的最重要障碍是血脑屏障的存在,它限制了血液与神经组织之间物质的运输。因此,需要开发足够的体外模型以表征候选药物进入中枢神经系统的渗透特性。这篇综述文章总结了基于脑内皮细胞培养的目前使用和最有希望的体外BBB模型。可以使用原代猪脑内皮细胞和啮齿动物共培养模型获得鲁棒的模型,这些模型具有较低的副细胞通透性并表达功能性外排转运蛋白,显示药物渗透数据与体内结果具有良好的相关性。还可以使用模仿BBB体内解剖生理学复杂性的模型,包括三重共培养(在周细胞和星形胶质细胞存在下培养脑血管内皮细胞),动态和微流体模型;但是,它们不适合用于快速,高通量的研究。易于获得且可重现的模型可能需要有效的人类细胞系,以避免种间差异。

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