title: Hemin-coupled iron(III)-hydroxide nanoparticles show increased uptake in Caco-2 cells.
abstract: OBJECTIVE
  The absorption of commonly used ferrous iron salts from intestinal segments at neutral to slightly alkaline pH is low, mainly because soluble ferrous iron is easily oxidized to poorly soluble ferric iron and ferrous iron but not ferric iron is carried by the divalent metal transporter DMT-1. Moreover, ferrous iron frequently causes gastrointestinal side effects. In iron(III)-hydroxide nanoparticles hundreds of ferric iron atoms are safely packed in nanoscaled cores surrounded by a solubilising carbohydrate shell, yet bioavailability from such particles is insufficient when compared with ferrous salts. To increase their intestinal uptake iron(III)-hydroxide nanoparticles were coupled in this study with the protoporphyrin hemin, which undergoes carrier-mediated uptake in the intestine.
  
  
  METHODS
  Uptake of iron(III)-hydroxide nanoparticles with hemin covalently coupled by DCC reaction was measured in Caco-2 cells with a colorimetric assay and visualized by transmission electron microscopy.
  
  
  RESULTS
  Nanoparticles were taken up by carrier-mediated transport, since uptake was temperature-dependent and increased with an increasing hemin substitution grade. Furthermore, uptake decreased with an increasing concentration of free hemin, due to competition for carrier-mediated uptake.
  
  
  CONCLUSIONS
  Hemin-coupled iron(III)-hydroxide nanoparticles were carried by a heme specific transport system, probably via receptor mediated endocytosis. It can be expected that this system shows improved absorption of iron compared with uncoupled iron(III)-hydroxide nanoparticles, which exist on the market today.
authors: Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors: Markus Richard
authors: MR
authors: Jahn
authors: Ibrahim
authors: I
authors: Shukoor
authors: Wolfgang
authors: W
authors: Tremel
authors: Uwe
authors: U
authors: Wolfrum
authors: Ute
authors: U
authors: Kolb
authors: Thomas
authors: T
authors: Nawroth
authors: Peter
authors: P
authors: Langguth
mesh_terms: D018938:Caco-2 Cells; D003124:Colorimetry; D004396:Coloring Agents; D003470:Culture Media; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism*; D005297:Ferrozine; D006427:Hemin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007502:Iron Chelating Agents; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D004396:Coloring Agents; D003470:Culture Media; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D005297:Ferrozine; C021024:ferric hydroxide; D006427:Hemin; C022616:thiazolyl blue