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关注点是它的 生物利用度部分由其在体内的吸收和代谢决定。 小肠。体外细胞中潜在有益药物的评价 在继续进行更复杂和更昂贵的工作之前，文化模式是必不可少的 动物研究。目前，来自人类结肠癌的Caco-2细胞是 用于研究药物在体外的转运。然而，该模型有几个 缺点。因此，我们建议检查一个体外模型，该模型包括 用于评估通透性的正常人体胃肠道细胞。初级阶段 该方案的目的是评估原代培养的肠上皮细胞的用途。 从小肠的三个区域获得用作模型的 胃肠道运输。分析将包括建立和 细胞接种密度、培养条件等条件的优化 以及获得所需汇合度所需的孵化时间 在单元插入物可用于传输分析之前。我们将使用 作为标准的电阻和渗透系数 建立紧密连接的完整性程度。建议的交通工具 模型应减少目前所需的组织培养时间、成本和工作量 在确定药物吸收和代谢差异方面非常有用。 遍布小肠各区域的各种化合物。 建议的商业应用：不可用