Oral uptake of nanoparticles: human relevance and the role of in vitro systems

Abstract

Nanoparticles (NPs) present in environment, consumer and health products, food and medical applications lead to a high degree of human exposure and concerns about potential adverse effects on human health. For the general population, the exposure through contact with the skin, inhalation and oral uptake are most relevant. Since in vivo testing is only partly able to study the effects of human oral exposure, physiologically relevant in vitro systems are being developed. This review compared the three routes taking into account the estimated concentration, size of the exposed area, morphology of the involved barrier and translocation rate. The high amounts of NPs in food, the large absorption area and the relatively high translocation rate identified oral uptake as most important portal of entry for NPs into the body. Changes of NP properties in the physiological fluids, mechanisms to cross mucus and epithelial barrier, and important issues in the use of laboratory animals for oral exposure are mentioned. The ability of in vitro models to address the varying conditions along the oro-gastrointestinal tract is discussed, and requirements for physiologically relevant in vitro testing of orally ingested NPs are listed.

Uptake of label-free graphene oxide by Caco-2 cells is dependent on the cell differentiation status

“…Nevertheless, even if enterocytes are the most abundant cell type of the intestinal barrier, the passage and uptake of GRM by other cell types found in the intestinal mucosa such as M-cells, goblet cells, enteroendocrine cells, Paneth cells as well as stem cells cannot be excluded and has to be determined in future investigations. Furthermore 2D- or 3D models composed of different cell types are needed to mimic the complexity of the intestinal barrier and to improve in vitro-in vivo correlation [26, 72, 73]. Models including intestinal microbes or considering the mechanical forces by peristalsis can further increase the physiological relevance.…”

Tissue distribution following 28 day repeated oral administration of aluminum‐based nanoparticles with different properties and the in vitro toxicity

“…Therefore, both the properties in the manufactured condition (primary) and the properties within the biological system (secondary) must be carefully considered in the interpretation of toxicity test results. First, shape and surface area are among the key factors in the determination of the toxicity of nanosized particles (Bakand, Hayes, & Dechsakulthom, 2012;Fröhlich & Roblegg, 2016;Li et al, 2015). In the current study, S-(2.1 ± 0.4) and…”

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals

“…Additional limitations of Caco-2 absorption experiments include the smaller tight junctions and a 10-fold thicker unstirred water layer compared with the in vivo situation (Hubatsch et al, 2007;Stenberg et al, 2001). Likewise, the absence of a mucus layer and so-called M-cells, which are involved in the uptake of particle matter, may result in inadequate transport measurements for some chemicals like nanoparticles (Fröhlich and Roblegg, 2016;Lefebvre et al, 2015;Walczak et al, 2015b). Nonspecific binding of highly lipophilic compounds to the plastic surfaces may result in a poor predictive value of highly lipophilic compounds (Hubatsch et al, 2007;Krishna et al, 2001;Neuhoff et al, 2006).…”