DEVELOPMENT OF AN IN VITRO BLOOD-BRAIN BARRIER

体外血脑屏障的发育

• 批准号: 3509268
• 负责人: SUSAN DOCTROW
• 金额: $ 25.07万
• 依托单位: ALKERMES, INC.
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3509268
• 关键词: biomaterial development /preparation; biotechnology; blood brain barrier; drug delivery systems; human tissue; intercellular connection; tissue /cell culture; vascular endothelium

The availability of pharmaceutical to combat neurological disorders is limited by the existence of the blood-brain barrier (BBB), a protective vascular system preventing most blood-borne molecules from entering the brain. Methods to transport drugs across the BBB would therefore be of enormous therapeutic and commercial value. The long-term goal of this project is to develop an in vitro model for the human BBB to serve as an experimental system for the discovery and evaluation of strategies for drug delivery to the brain. This model will consist of human brain microvascular endothelial cell cultures expressing BBB-associated properties. Phase i feasibility studies, in which these cells were isolated and grown on porous substrata, led to preliminary identification of culture conditions inducing the cell monolayer to restrict solute diffusion. Building upon these data, the development of an in vitro human BBB will continue in Phase II. The first aim will be to define the optimal culture environment for the in vitro human BBB, by screening culture components to identify those that promote the most restrictive cell monolayer. Once one or more culture conditions have been chosen, further studies will characterize the in vitro human BBB by testing it for several properties exhibited by the authentic BBB. These will include BBB-associated proteins, detected with immunological and functional assays, tight junctions, examined by electron microscopy, and specific transport systems that, in vivo, allow the brain to receive essential nutrients. These studies, by addressing the extent to which the in vitro human BBB mimics the BBB in vivo, should facilitate research, in Phase III and beyond, to apply this model as an experimental system for the design and testing of innovative drug delivery systems that circumvent the BBB.

治疗神经系统疾病的药物的可用性 由于血脑屏障（BBB）的存在， 血管系统阻止大多数血液传播的分子进入 个脑袋 因此，运输药物穿过BBB的方法将是： 巨大的医疗和商业价值。 长期目标是 项目是开发一种体外模型，用于人类血脑屏障， 用于发现和评估以下策略的实验系统： 药物输送到大脑。 这个模型将由人脑组成 微血管内皮细胞培养表达血脑屏障相关 特性. 第一阶段可行性研究，其中这些细胞是 分离并生长在多孔基质上， 诱导细胞单层的培养条件的鉴定 限制溶质扩散。 根据这些数据， 体外人血脑屏障将在II期继续进行。 第一个目标是 为了确定体外人血脑屏障的最佳培养环境， 筛选培养成分，以确定那些促进最 限制性细胞单层。 一旦一种或多种培养条件 选择后，进一步的研究将通过以下方式表征体外人BBB： 测试它的几个属性所表现出的真正的血脑屏障。 这些 将包括BBB相关蛋白，用免疫学和 功能测定，紧密连接，通过电子显微镜检查， 特定的运输系统，在体内允许大脑接收 必需营养素 这些研究通过探讨 体外人血脑屏障模拟体内血脑屏障， 研究，在第三阶段及以后，应用这一模型作为一个 创新药物设计与检测实验系统 绕过BBB的递送系统。