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

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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.