title: 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.
authors.affiliation: Center for Medical Research, Medical University of Graz, Stiftingtalstr. 24, 8010, Graz, Austria. Eleonore.froehlich@medunigraz.at.
authors.forename: Eleonore
authors.identifier: http://orcid.org/0000-0002-6056-6829
authors.initials: E
authors.lastname: Fröhlich
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, Graz, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Roblegg
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport; D003257:Consumer Product Safety; D004781:Environmental Exposure / Q000032:analysis*; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005506:Food Contamination / Q000032:analysis; D065569:Gastrointestinal Absorption / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D010316:Particle Size; D065589:Respiratory Tract Absorption / Q000187:drug effects; D012869:Skin Absorption / Q000187:drug effects; D013045:Species Specificity; D013499:Surface Properties
chemical_list: D004785:Environmental Pollutants
keywords: Barrier models; Consumer products; Exposure doses; Inter-species differences; Oro-gastrointestinal tract