Impact of Lipids On Intestinal Mucus Transport And Structural Properties

脂质对肠粘液运输和结构特性的影响

基本信息

  • 批准号:
    8386074
  • 负责人:
  • 金额:
    $ 23.39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-08-01 至 2014-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this project is to elucidate the impact of lipids and food-associated physicochemical changes in the gastrointestinal (GI) tract on intestinal mucus barrier properties. This information will motivate strategies for mucosal barrier control, enabling efficient drug carrier systems (e.g. mucosal vaccines), enhanced nutrition, and potentially inhibited pathogen invasion. Gastrointestinal mucus is a natural hydrogel providing a finely-tuned and amazingly selective barrier, protecting the underlying epithelium from harsh physicochemical changes in the intestinal lumen (e.g. elevations in bile salt concentration, lowered pH), selectively inhibiting microbial transport, and enabling efficient absorption of nutrients and water. Despite the significance of mucus's role and potential implications in health and disease, its barrier properties are relatively poorly understood. Preliminary data indicates that intestinal mucus properties are significantly modulated by food-associated lipids and physicochemical changes associated with food (i.e. changes in pH and [Ca+2 ]). To study these phenomena and enable design of strategies to exploit them for therapeutic purposes, the transport of micro-particulates, model microbes and small molecular weight compounds will be analyzed using multiple particle tracking techniques and a novel application of electron paramagnetic resonance (EPR). Particles, microbes and compounds will be exposed to mucus surfaces in media containing food-associated lipids as well as model fasted state intestinal buffer, at varied pH and Ca+2 concentrations. These analyses will be performed on both native mucus as well as purified mucin gels to provide insight into mucus structural components responding to specific food-associated stimuli. Micro- and macro-rheological analyses performed in parallel will indicate the relative significance of mucus gel structural changes vs. interactions occurring between particles/molecules and gel constituents in observed transport phenomena. Structural changes in mucus gels associated with exposure to food-associated lipids and physicochemical environmental changes will also be examined using advanced microscopic techniques, including quick-freeze deep etch microscopy (QF/DEM). The integrity of colloidal structures formed by food-associated lipids within the mucus layer will be examined using EPR and nitroxide-probe labeled bile salts and lipids, as it is currently not understood whether these structures stay intact within mucus, which could significantly impact the nature of transport through this natural hydrogel. The interdisciplinary research team possesses the expertise required to successfully understand and begin to exploit the impact of lipids on the GI mucus barrier, including the PI, a chemical engineer with expertise in transport phenomena in drug delivery and mucus, a biochemist with expertise in pathogen transport through mucus and mucus theology, a mechanical engineer with expertise in advanced microscopic analysis of biological matrix structure, and a chemist with expertise in electron paramagnetic resonance analysis of small molecule mobility in membranes. PUBLIC HEALTH RELEVANCE: This project will provide insight into mucus barrier property modulation with food-associated lipids and physiological changes (i.e. reduction in pH, [Ca+2] elevation). This information will enable enhanced understanding of nutrient absorption and microbial mobility at intestinal mucosal surfaces and development of novel technologies exploiting natural mucus barrier modulation mechanisms to enhance drug carrier transport and nutrient uptake, and potentially control pathogen invasion.
描述(由申请人提供):本项目的总体目标是阐明胃肠道中脂类和食物相关的物理化学变化对肠道粘液屏障特性的影响。这一信息将激发粘膜屏障控制策略,实现有效的药物载体系统(如粘膜疫苗),增强营养,并潜在地抑制病原体入侵。胃肠道粘液是一种天然的水凝胶,提供了一种微调和惊人的选择性屏障,保护下层上皮免受肠道内剧烈的物理化学变化(如胆汁盐浓度升高,pH值降低),选择性地抑制微生物运输,并使其高效

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Rebecca L Carrier其他文献

Rebecca L Carrier的其他文献

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{{ truncateString('Rebecca L Carrier', 18)}}的其他基金

Rationally designed lipid- and food-based drug formulations to enhance oral bioavailability
合理设计脂质和食品药物配方,提高口服生物利用度
  • 批准号:
    10157659
  • 财政年份:
    2021
  • 资助金额:
    $ 23.39万
  • 项目类别:
GuMI: New In Vitro Platforms to Parse the Human Gut Epithelial-Microbiome-Immune Axis
GuMI:解析人类肠道上皮-微生物组-免疫轴的新体外平台
  • 批准号:
    9071777
  • 财政年份:
    2016
  • 资助金额:
    $ 23.39万
  • 项目类别:
GuMI: New In Vitro Platforms to Parse the Human Gut Epithelial-Microbiome-Immune Axis
GuMI:解析人类肠道上皮-微生物组-免疫轴的新体外平台
  • 批准号:
    9923719
  • 财政年份:
    2016
  • 资助金额:
    $ 23.39万
  • 项目类别:
Impact of lipids and food on oral compound absorption: mechanistic studies and modeling
脂质和食物对口服化合物吸收的影响:机制研究和建模
  • 批准号:
    10201616
  • 财政年份:
    2012
  • 资助金额:
    $ 23.39万
  • 项目类别:
Impact of Lipids on Compound Absorption: Mechanistic Studies and Modeling
脂质对化合物吸收的影响:机理研究和建模
  • 批准号:
    8265112
  • 财政年份:
    2012
  • 资助金额:
    $ 23.39万
  • 项目类别:
Impact of Lipids On Intestinal Mucus Transport And Structural Properties
脂质对肠粘液运输和结构特性的影响
  • 批准号:
    8518101
  • 财政年份:
    2012
  • 资助金额:
    $ 23.39万
  • 项目类别:
Impact of Lipids on Compound Absorption: Mechanistic Studies and Modeling
脂质对化合物吸收的影响:机理研究和建模
  • 批准号:
    8650903
  • 财政年份:
    2012
  • 资助金额:
    $ 23.39万
  • 项目类别:
Impact of Lipids on Compound Absorption: Mechanistic Studies and Modeling
脂质对化合物吸收的影响:机理研究和建模
  • 批准号:
    8828234
  • 财政年份:
    2012
  • 资助金额:
    $ 23.39万
  • 项目类别:
Impact of Lipids on Compound Absorption: Mechanistic Studies and Modeling
脂质对化合物吸收的影响:机理研究和建模
  • 批准号:
    8494643
  • 财政年份:
    2012
  • 资助金额:
    $ 23.39万
  • 项目类别:
Interphotoreceptor Matrix Based Cell Delivery Vehicle for Retinal Regeneration
用于视网膜再生的基于光感受器间基质的细胞递送载体
  • 批准号:
    8032073
  • 财政年份:
    2011
  • 资助金额:
    $ 23.39万
  • 项目类别:

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