title: The gut wall provides an effective barrier against nanoparticle uptake.
abstract: BACKGROUND
  The omnipresence of nanoparticles (NPs) in numerous goods has led to a constant risk of exposure and inadvertent uptake for humans. This situation calls for thorough investigation of the consequences of NP intake. As the vast mucosa of the human gastrointestinal tract represents an attractive site of entry, we wanted to take a look on the fate that ingested NPs suffer in the gut. As a model to investigate NP uptake we used the isolated perfused rat small intestine. Differently sized fluorescent latex particles were used as exemplary anthropogenic NPs.
  
  
  RESULTS
  The particles were administered as bolus into the isolated intestine, and samples from the luminal, vascular and lymphatic compartments were collected over time. NP amounts in the different fluids were determined by fluorescence measurements. No particles could be detected in the vascular and lymphatic system. By contrast a major amount of NPs was found in luminal samples. Yet, a substantial share of particles could not be recovered in the fluid fractions, indicating a sink function of the intestinal tissue for NPs. A histological examination of the gut revealed that virtually no particles adhered to the epithelium or resided in the tissue, the bulk of particles seemed to be trapped in the mucus lining the gut tube. When this mucus was dissolved and removed from the gut almost the entire amount of particles missing could be recovered: over 95% of the given NPs were present in the two fractions, the luminal samples and the dissolved mucus. To foster NP uptake via an extended interaction time with the epithelium, the intestinal peristalsis was decelerated and the duration of the experiment was prolonged. Even under those conditions, no particle fluorescence was detected in the vascular and lymphatic samples.
  
  
  CONCLUSIONS
  We could show that after intestinal exposure with a large dose of NPs the vast majority of NPs did obviously not come into contact with the epithelium but was either directly discarded from the gut or trapped in mucus. The healthy small intestinal tract evidently provides an effective barrier against NP uptake whereby the mucus film seems to play an important role.
authors.affiliation: Division of Mucosal Immunology & Diagnostics, Priority Program Asthma & Allergy, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Parkallee 22, Borstel, 23845, Germany, Airway Research Center North (ARCN), Member of the German Center for Lung Research.
authors.forename: Heike
authors.initials: H
authors.lastname: Sinnecker
authors.affiliation: Division of Mucosal Immunology & Diagnostics, Priority Program Asthma & Allergy, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Parkallee 22, Borstel, 23845, Germany, Airway Research Center North (ARCN), Member of the German Center for Lung Research.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Krause
authors.affiliation: Central Laboratory of Analytical Chemistry, Hamburg University of Technology, Eißendorfer Straße 38, Hamburg, 21073, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Koelling
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Schwanenweg 21, Kiel, 24105, Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Lautenschläger
authors.affiliation: Division of Mucosal Immunology & Diagnostics, Priority Program Asthma & Allergy, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Parkallee 22, Borstel, 23845, Germany, Airway Research Center North (ARCN), Member of the German Center for Lung Research.
authors.forename: Andreas
authors.initials: A
authors.lastname: Frey
keywords: barrier; isolated intestine; mucus; nanoparticles; uptake