DYNAMIC MODEL FOR THE HIV BLOOD BRAIN BARRIER

HIV 血脑屏障的动态模型

• 批准号: 2830700
• 负责人: JAMES B HICKS
• 金额: $ 9.8万
• 依托单位: VIROGENOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2830700
• 关键词: 2'3' dideoxyinosine; AIDS dementia complex; AIDS therapy; HIV infections; antiAIDS agent; astrocytes; bioengineering /biomedical engineering; biological transport; blood brain barrier; disease /disorder model; drug screening /evaluation; human immunodeficiency virus 1; mixed tissue /cell culture; model design /development; neuropharmacology; nucleoside analog; pharmacokinetics; zidovudine

The purpose of this project is to establish a commercially viable, in vitro disease model for the blood-brain barrier in AIDS dementia complex (ADC) and system for testing anti-HIV drugs in vitro. This model will be useful for examining the penetration of HIV antiviral drugs through the infected and uninfected blood-brain barrier and for testing the efficacy of candidate drugs on HIV in infected brain endothelium. These studies can be expanded to investigations of drug permeation to the CNS in general and are not limited to the delivery of anti-retroviral agents. The in vitro model employs brain microvascular endothelial cells cultured in hollow fiber capillaries surrounded by astroglia to induce a tri- dimensional barrier with flow through the vessel lumen. Culture medium is pumped through the luminal and abluminal spaces separately allowing measurement of molecular traffic across the barrier. This dynamic in vitro blood-brain barrier model (DIV-BBB) reproduces the physiology of the BBB in vivo including specific ion and molecular transport systems not available in other in vitro models. PROPOSED COMMERCIAL APPLICATIONS: Establish a scientific validation of a system (equipment, cells, techniques) that can be used to test candidate drugs on contract for their ability to penetrate the human blood-brain barrier and to have efficacy against HIV in vivo. The product will be both the test system itself and the service of testing compounds for pharmaceutical companies.

该项目的目的是建立一个商业可行的 艾滋病痴呆症复合物中血脑屏障的体外疾病模型 （ADC）和用于在体外测试抗HIV药物的系统。这个模型将是 可用于检查HIV抗病毒药的渗透 感染和未感染的血脑屏障，用于测试功效 感染脑内皮中HIV的候选药物。这些研究 可以扩展到对CNS药物渗透的调查 一般，不仅限于抗逆转录病毒药物的递送。 体外模型采用培养的脑微血管内皮细胞 在被星形胶质细胞包围的空心纤维毛细管中，以诱导三 尺寸屏障，流过容器管腔。培养基 分别通过腔内和排放空间泵送 测量整个屏障的分子流量。这种动态 体外血脑屏障模型（DIV-BBB）再现 BBB体内包括特定离子和分子传输系统 在其他体外模型中不可用。 拟议的商业应用： 建立对系统的科学验证（设备，牢房， 技术）可用于在合同上测试候选药物 他们能够穿透人类血脑屏障并拥有 对艾滋病毒在体内的疗效。该产品将是测试系统 本身以及为制药公司的测试化合物服务。