title: In vitro placental model optimization for nanoparticle transport studies.
abstract: BACKGROUND
  Advances in biomedical nanotechnology raise hopes in patient populations but may also raise questions regarding biodistribution and biocompatibility, especially during pregnancy. Special consideration must be given to the placenta as a biological barrier because a pregnant woman's exposure to nanoparticles could have significant effects on the fetus developing in the womb. Therefore, the purpose of this study is to optimize an in vitro model for characterizing the transport of nanoparticles across human placental trophoblast cells.
  
  
  METHODS
  The growth of BeWo (clone b30) human placental choriocarcinoma cells for nanoparticle transport studies was characterized in terms of optimized Transwell(®) insert type and pore size, the investigation of barrier properties by transmission electron microscopy, tight junction staining, transepithelial electrical resistance, and fluorescein sodium transport. Following the determination of nontoxic concentrations of fluorescent polystyrene nanoparticles, the cellular uptake and transport of 50 nm and 100 nm diameter particles was measured using the in vitro BeWo cell model.
  
  
  RESULTS
  Particle size measurements, fluorescence readings, and confocal microscopy indicated both cellular uptake of the fluorescent polystyrene nanoparticles and the transcellular transport of these particles from the apical (maternal) to the basolateral (fetal) compartment. Over the course of 24 hours, the apparent permeability across BeWo cells grown on polycarbonate membranes (3.0 μm pore size) was four times higher for the 50 nm particles compared with the 100 nm particles.
  
  
  CONCLUSIONS
  The BeWo cell line has been optimized and shown to be a valid in vitro model for studying the transplacental transport of nanoparticles. Fluorescent polystyrene nanoparticle transport was size-dependent, as smaller particles reached the basal (fetal) compartment at a higher rate.
authors.affiliation: Bristol Initiative for Research of Child Health, Biophysics Research Unit, St Michael's Hospital, UH Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Cartwright
authors.forename: Marie Sønnegaard
authors.initials: MS
authors.lastname: Poulsen
authors.forename: Hanne Mørck
authors.initials: HM
authors.lastname: Nielsen
authors.forename: Giulio
authors.initials: G
authors.lastname: Pojana
authors.forename: Lisbeth E
authors.initials: LE
authors.lastname: Knudsen
authors.forename: Margaret
authors.initials: M
authors.lastname: Saunders
authors.forename: Erik
authors.initials: E
authors.lastname: Rytting
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011076:Polycarboxylate Cement / Q000737:chemistry / Q000493:pharmacokinetics; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics; D016062:Porosity; D011247:Pregnancy; D015203:Reproducibility of Results; D057900:Transcytosis / Q000187:drug effects*; D014594:Uterine Neoplasms / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D005456:Fluorescent Dyes; D008565:Membrane Proteins; D010750:Phosphoproteins; D011076:Polycarboxylate Cement; D011091:Polyesters; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C005506:polycarbonate