It takes more than a coating to get nanoparticles through the intestinal barrier in vitro

Eur J Pharm Biopharm. 2017 Sep:118:21-29. doi: 10.1016/j.ejpb.2016.12.004. Epub 2016 Dec 18.

Abstract

Size and shape are crucial parameters which have impact on the potential of nanoparticles to penetrate cell membranes and epithelial barriers. Current research in nanotoxicology additionally focuses on particle coating. To distinguish between core- and coating-related effects in nanoparticle uptake and translocation, two nanoparticles equal in size, coating and charge but different in core material were investigated. Silver and iron oxide nanoparticles coated with poly (acrylic acid) were chosen and extensively characterized by small-angle x-ray scattering, nanoparticle tracing analysis and transmission electron microscopy (TEM). Uptake and transport were studied in the intestinal Caco-2 model in a Transwell system with subsequent elemental analysis. TEM and ion beam microscopy were conducted for particle visualization. Although equal in size, charge and coating, the behavior of the two particles in Caco-2 cells was different: while the internalized amount was comparable, only iron oxide nanoparticles additionally passed the epithelium. Our findings suggest that the coating material influenced only the uptake of the nanoparticles whereas the translocation was determined by the core material. Knowledge about the different roles of the particle coating and core materials in crossing biological barriers will facilitate toxicological risk assessment of nanoparticles and contribute to the optimization of pharmacokinetic properties of nano-scaled pharmaceuticals.

Keywords: Caco-2; Ion beam microscopy; Iron oxide; Poly (acrylic-acid); Silver; TEM; Transwell™ system.

MeSH terms

  • Acrylic Resins / chemistry*
  • Caco-2 Cells
  • Cell Culture Techniques
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Cell Membrane Permeability
  • Coated Materials, Biocompatible / administration & dosage
  • Coated Materials, Biocompatible / chemistry
  • Coated Materials, Biocompatible / metabolism*
  • Enterocytes / metabolism*
  • Enterocytes / ultrastructure
  • Ferric Compounds / administration & dosage
  • Ferric Compounds / chemistry
  • Ferric Compounds / metabolism
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Microscopy, Electron, Transmission
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Particle Size
  • Permeability
  • Scattering, Small Angle
  • Silver / administration & dosage
  • Silver / chemistry
  • Silver / metabolism
  • X-Ray Diffraction

Substances

  • Acrylic Resins
  • Coated Materials, Biocompatible
  • Ferric Compounds
  • ferric oxide
  • Silver
  • carbopol 940