Novel biomaterials for IBD treatment

用于治疗 IBD 的新型生物材料

• 批准号: 10393539
• 负责人: Nobuhiko Kamada
• 金额: $ 63.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393539
• 关键词: Acute; Adult; Affect; American; Benchmarking; Bilirubin; Binding; Biocompatible Materials; Biological Products; CD44 gene; Cells; Colitis; Colon; Colonic inflammation; Diagnosis; Disease; Drug Delivery Systems; Drug Targeting; Epithelial; Germ-Free; Goals; Human; Hyaluronic Acid; Immune; Immunosuppressive Agents; Infection; Inflammatory; Inflammatory Bowel Diseases; Interleukin-1 beta; Interleukin-6; Intestines; Knowledge; Mononuclear; Mus; Natural Immunity; Oral Administration; Phagocytes; Pharmaceutical Preparations; Property; Regulation; Research; Role; System; TNF gene; Therapeutic; Translations; Transplantation; Treatment Efficacy; base; commensal bacteria; commensal microbes; cytokine; design; drug development; early phase clinical trial; fecal transplantation; frontier; gastrointestinal epithelium; gut inflammation; gut microbiome; gut microbiota; healing; human microbiota; humanized mouse; immunosuppressed; intestinal barrier; macrophage; microbiome therapeutics; microbiota; monocular; monocyte; mouse model; nanoformulation; nanoparticle; novel; novel strategies; response; restoration; symptom treatment

Abstract Over 3 million U.S. adults are diagnosed with inflammatory bowel disease (IBD). The current IBD therapies, such as immunosuppressants and biologics, treat the symptoms of IBD; however, they generally do not address the underlying causes, including defective intestinal barrier functions, abnormal levels of pro-inflammatory cytokines and immune cells, and dysregulated gut commensal microbes. Thus, there exists a critical need for new approaches for treatment of IBD. Moreover, gut microbiome is emerging as the next frontier in drug development. However, it remains unknown how to effectively regulate the gut microbiome for therapeutic purposes. Our long- term research goal is to develop new gut-targeted strategies for modulating innate immunity and gut microbiome. Our objectives in this application is to generate new fundamental knowledge on biomaterial parameters for efficient targeting of inflamed colon and subsequent restoration of intestinal barrier functions and healthy gut microbiota in IBD. Toward this goal, we have developed a new biomaterial system that can target inflamed colon and initiate healing responses in inflamed colonic epithelium. Here, using our biomaterial system as a starting platform, we seek to uncover new materials criteria for designing biomaterials for optimal colon targeting (Aim 1), regulation of innate immunity (Aim 2), and modulation of the gut microbiota (Aim 3) in the context of IBD. Overall, successful completion of our proposal will enable colon-targeted drug delivery systems that will exert potent efficacy against IBD.

抽象的 超过 300 万美国成年人被诊断患有炎症性肠病 (IBD)。目前的 IBD 治疗方法包括 作为免疫抑制剂和生物制剂，治疗 IBD 症状；然而，它们一般不涉及 根本原因，包括肠道屏障功能缺陷、促炎细胞因子水平异常 和免疫细胞，以及失调的肠道共生微生物。因此，迫切需要新的 IBD 的治疗方法。此外，肠道微生物组正在成为药物开发的下一个前沿领域。 然而，如何有效调节肠道微生物组以达到治疗目的仍然未知。我们的长期 学期研究目标是开发新的肠道靶向策略来调节先天免疫和肠道微生物组。 我们在此应用中的目标是生成有关生物材料参数的新基础知识 有效靶向发炎的结肠，随后恢复肠道屏障功能和健康的肠道 IBD 中的微生物群。为了实现这一目标，我们开发了一种新的生物材料系统，可以针对发炎的结肠 并启动发炎的结肠上皮的愈合反应。在这里，使用我们的生物材料系统作为起点 平台上，我们寻求发现设计生物材料以实现最佳结肠靶向的新材料标准（目标 1)、先天免疫的调节（目标 2），以及 IBD 背景下肠道微生物群的调节（目标 3）。 总的来说，我们提案的成功完成将使结肠靶向药物输送系统能够发挥作用 对 IBD 具有强大的功效。