title: Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental Barrier in an ex Vivo Human Placental Perfusion Model.
abstract: BACKGROUND
  Nanoparticle exposure in utero might not be a major concern yet, but it could become more important with the increasing application of nanomaterials in consumer and medical products. Several epidemiologic and in vitro studies have shown that nanoparticles can have potential toxic effects. However, nanoparticles also offer the opportunity to develop new therapeutic strategies to treat specifically either the pregnant mother or the fetus. Previous studies mainly addressed whether nanoparticles are able to cross the placental barrier. However, the transport mechanisms underlying nanoparticle translocation across the placenta are still unknown.
  
  
  OBJECTIVE
  In this study we examined which transport mechanisms underlie the placental transfer of nanoparticles.
  
  
  METHODS
  We used the ex vivo human placental perfusion model to analyze the bidirectional transfer of plain and carboxylate modified polystyrene particles in a size range between 50 and 300 nm.
  
  
  RESULTS
  We observed that the transport of polystyrene particles in the fetal to maternal direction was significantly higher than for the maternal to fetal direction. Regardless of their ability to cross the placental barrier and the direction of perfusion, all polystyrene particles accumulated in the syncytiotrophoblast of the placental tissue.
  
  
  CONCLUSIONS
  Our results indicate that the syncytiotrophoblast is the key player in regulating nanoparticle transport across the human placenta. The main mechanism underlying this translocation is not based on passive diffusion, but is likely to involve an active, energy-dependent transport pathway. These findings will be important for reproductive toxicology as well as for pharmaceutical engineering of new drug carriers.
authors.affiliation: Laboratory for Particles-Biology Interactions, Empa, St. Gallen, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Grafmueller
authors.forename: Pius
authors.initials: P
authors.lastname: Manser
authors.forename: Liliane
authors.initials: L
authors.lastname: Diener
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Diener
authors.forename: Xenia
authors.initials: X
authors.lastname: Maeder-Althaus
authors.forename: Lionel
authors.initials: L
authors.lastname: Maurizi
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.forename: Harald F
authors.initials: HF
authors.lastname: Krug
authors.forename: Tina
authors.initials: T
authors.lastname: Buerki-Thurnherr
authors.forename: Ursula
authors.initials: U
authors.lastname: von Mandach
authors.forename: Peter
authors.initials: P
authors.lastname: Wick
mesh_terms: D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D053758:Nanoparticles; D010316:Particle Size; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011137:Polystyrenes / Q000493:pharmacokinetics*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D011137:Polystyrenes