Fabrication of Nanoscale Plastics and Effects on Intestinal Barrier Function In Vitro

纳米塑料的制备及其对体外肠道屏障功能的影响

• 批准号: 10524902
• 负责人: TIMOTHY RAYMOND FENNELL
• 金额: $ 33.35万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524902
• 关键词: Address; Affect; Animal Model; Beverages; Biological; Cell model; Cells; Chemicals; Coculture Techniques; Complex; Data; Digestion; Dose; Ensure; Enterocytes; European; Exploratory/Developmental Grant; Feces; Food; Food Chain; Food Safety; Formulation; Goals; Goblet Cells; Health; Human; In Vitro; Ingestion; International; Intestines; Investigation; Joints; Label; M cell; Mammalian Cell; Manuscripts; Methods; Modeling; Nylons; Oral Ingestion; Particle Size; Permeability; Physiological; Plastics; Polyethylene Terephthalates; Polyethylenes; Polymers; Polypropylenes; Polystyrenes; Preparation; Principal Investigator; Property; Reporting; Research; Research Personnel; Risk; Route; Sampling; Schools; Small Intestines; Statistical Data Interpretation; Testing; Tight Junctions; Time; Tracer; World Health; World Health Organization; authority; biological systems; biomaterial compatibility; cost; cytotoxic; density; design; drinking water; experience; in vitro Assay; in vitro Model; intestinal barrier; macrophage; monolayer; nanoengineering; nanomaterials; nanoscale; nanoscience; nanotoxicology; particle; response; success; uptake

PROJECT SUMMARY/ABSTRACT The overarching goal of this proposed R21 program is to fabricate well-characterized nanoplastics (NPs) comprising high-commodity plastics and to investigate the impact of these NPs on intestinal barrier function in vitro. This proposed research addresses the numerous reports showing that drinking water, beverages, and food products contain small-scale fragmented plastics (microplastics or MPs and likely NPs) consisting of high-commodity plastics (e.g., polyethylene terephthalate [PET], polyamide [Nylon], high- and low-density polyethylene [HDPE and LDPE, respectively], polypropylene [PP]). However, current conclusions concerning the effects of NPs on biological systems are primarily deduced from studies using commercially available polystyrene (PS), which does not represent the breadth of globally dominant plastics. Unfortunately, NPs derived from the most common globally manufactured polymers are unavailable, either commercially or via fabrication routes, thereby impeding biological studies similar to those already performed with PS. This R21 program addresses the critical need for scientific data to understand human health risks from the unintentional ingestion of NPs, a need that has been emphasized by both the World Health Organization and European Food Safety Authority. We will design and develop well-characterized NPs comprising globally ubiquitous plastics that have not been fabricated previously or tested in mammalian cells or animal models before. Our design strategy will ensure that the fabricated NPs are appropriate for systematic biological studies that require tracers, tight particle size distributions, and well-characterized compositions. Our approach will result in the first studies using in vitro models to examine how NPs derived from the most common high-commodity plastics affect intestinal barrier function. The overarching hypothesis is that NPs comprising globally ubiquitous plastics can interact with the intestinal barrier and affect the barrier function of the small intestinal tract. We propose two specific aims: (1) develop highly characterized NPs comprising high-commodity plastics that are suitable for assessment in biological systems and (2) evaluate NP digestion, translocation, and interference with the small intestinal tract in vitro. To assess the human health risk of NPs, scientific data are needed, and investigating the impact of digested NPs on intestinal barrier function is a critical first step. This R21 program is milestone-driven and provides defined deliverables to support steps toward understanding how the unintentional ingestion of NPs affects human health.

项目摘要/摘要 该提议的R21程序的总体目标是制造特征良好的纳米塑料（NPS） 包括高商品塑料并研究这些NP对肠屏障的影响 体外功能。这项拟议的研究涉及众多报告，表明饮用水， 饮料，食品中含有小规模的碎片塑料（微塑料或MPS，并且可能 NPS）由高商品塑料（例如聚对苯二甲酸酯[PET]，聚酰胺[尼龙]， 高密度聚乙烯[HDPE和LDPE]，聚丙烯[PP]）。但是，当前 关于NP对生物系统影响的结论主要是从研究中得出的 市售的聚苯乙烯（PS），不代表全球占主导地位的广度 塑料。不幸的是，源自全球最常见的聚合物的NP是 无论是在商业上还是通过制造路线，都无法使用，从而阻碍了类似的生物学研究 那些已经与PS一起执行的。该R21程序解决了科学数据的关键需求 从无意中摄入NPS中了解人类健康的风险，这一需求已得到强调 由世界卫生组织和欧洲食品安全局。我们将设计和开发 特征良好的NP，包括以前尚未制造的全球无处不在塑料或 以前在哺乳动物细胞或动物模型中进行了测试。我们的设计策略将确保捏造 NP适用于需要示踪剂，紧密粒度分布的系统生物学研究， 和良好的构图。我们的方法将导致最初使用体外模型的研究 检查最常见的高商品塑料的NP如何影响肠道屏障 功能。总体假设是，包括全球无处不在塑料的NP可以与 肠屏障并影响小肠道的屏障功能。我们提出了两个特定的 目的：（1）开发出适用于高商品塑料的高度特征的NP 评估生物系统和（2）评估NP消化，易位和干扰 体外小肠道。为了评估NP的人类健康风险，需要科学数据，并且 研究消化NP对肠屏障功能的影响是关键的第一步。这个R21 程序是里程碑式驱动的，并提供了定义的可交付成果，以支持了解如何了解的步骤 NP的无意摄入会影响人类健康。