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.

项目概要/摘要 该 R21 计划的总体目标是制造特征良好的纳米塑料 (NP) 包含高级塑料并研究这些纳米颗粒对肠道屏障的影响 体外发挥作用。这项拟议的研究涉及大量报告，表明饮用水、 饮料和食品含有小规模塑料碎片（微塑料或 MP 以及可能的塑料碎片） NP）由高品质塑料（例如聚对苯二甲酸乙二醇酯 [PET]、聚酰胺 [尼龙]、 高密度聚乙烯和低密度聚乙烯 [分别为 HDPE 和 LDPE]、聚丙烯 [PP]）。然而，目前 关于纳米粒子对生物系统影响的结论主要是从使用以下方法的研究中得出的： 市售聚苯乙烯（PS），并不代表全球主导的广度 塑料。不幸的是，源自全球最常见聚合物的纳米粒子 无论是商业上还是通过制造途径都无法获得，从而阻碍了类似于 那些已经用PS表演过的。该 R21 计划满足了对科学数据的迫切需求 了解无意摄入纳米粒子造成的人类健康风险，这一需求已得到强调 由世界卫生组织和欧洲食品安全局共同制定。我们将设计和开发 特征明确的纳米粒子，由全球普遍存在的塑料组成，以前从未制造过或 之前在哺乳动物细胞或动物模型中进行过测试。我们的设计策略将确保制造的 NP 适用于需要示踪剂、紧密粒径分布、 和特征鲜明的作品。我们的方法将导致第一个使用体外模型的研究 研究从最常见的高级塑料中提取的纳米粒子如何影响肠道屏障 功能。总体假设是，由全球普遍存在的塑料组成的纳米粒子可以与 破坏肠道屏障并影响小肠的屏障功能。我们提出两个具体方案 目标：（1）开发由高品质塑料组成的高度特征化的纳米颗粒，适用于 生物系统中的评估和（2）评估 NP 消化、易位和对 体外小肠。为了评估纳米粒子对人类健康的风险，需要科学数据，并且 研究消化的纳米粒子对肠道屏障功能的影响是关键的第一步。这个R21 该计划是里程碑驱动的，并提供定义的可交付成果来支持了解如何 无意摄入纳米粒子会影响人类健康。