DEVELOPMENT OF GASTROINTESTINAL TRANSPORT MODELS

胃肠道运输模型的开发

• 批准号: 6339833
• 负责人: MARY PAT MOYER
• 金额: $ 10万
• 依托单位: INCELL CORPORATION, LLC
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6339833
• 关键词: biological models; drug metabolism; gastrointestinal drug absorption; gastrointestinal epithelium; membrane permeability; model design /development; morphology; tissue /cell culture

DESCRIPTION (Applicant's Abstract): A major concern of any new drug is its bioavailability determined in part by its absorption and metabolism in the small intestine. Evaluation of potentially beneficial drugs in an in vitro cell culture model is essential before proceeding with more elaborate and expensive animal studies. Currently, Caco-2 cells derived from a human colon cancer are used to study drug transport in vitro. However, this model has several drawbacks. Therefore, we propose to examine an in vitro model consisting of normal human gastrointestinal cells for assessing permeability. The primary goal of this proposal is to evaluate the use of primary culture enterocytes obtained from the three regions of small intestine for use as models of gastrointestinal transport. Analyses will include establishment and optimization of conditions such as cell seeding densities, culture conditions and time of incubation required to obtain a level of confluence necessary before the cell inserts can be used for transport analysis. We will use electrical resistance and permeability coefficients as criteria for establishing the degree to tight junction integrity. The proposed transport models should reduce tissue culture time, cost and effort currently required and be very useful in determining absorption and metabolism differences of various compounds throughout the regions of the small intestine. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（申请人摘要）：任何新药的一个主要问题是其 生物利用度部分由其在体内的吸收和代谢决定。 小肠在体外细胞中评估潜在有益药物 在进行更精细和昂贵的 动物研究。目前，来源于人结肠癌的Caco-2细胞是 用于研究体外药物转运。然而，这种模式有几个 缺点.因此，我们建议检查由以下组成的体外模型 正常人胃肠道细胞用于评估渗透性。主 本提案的目的是评估原代培养肠上皮细胞的使用 从小肠的三个区域获得，用作 胃肠道转运分析将包括建立和 优化条件如细胞接种密度、培养条件 以及获得所需融合水平所需的孵育时间 在细胞插入物可用于运输分析之前。我们将使用 电阻和渗透系数作为标准， 建立紧密连接完整性的程度。拟议的运输 模型应减少组织培养时间，成本和努力目前需要的 并且在确定药物的吸收和代谢差异方面非常有用， 各种化合物遍布小肠的各个区域。 拟议商业应用：不可用