In vitro placental model optimization for nanoparticle transport studies

Laura Cartwright, Marie Sønnegaard Poulsen, Hanne Mørck Nielsen, Giulio Pojana, Lisbeth E. Knudsen, Margaret Saunders, Erik Rytting

Research output: Contribution to journalArticle

57 Scopus citations

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 signifcant 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 fuorescein sodium transport. Following the determination of nontoxic concentrations of fuorescent 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, fuorescence readings, and confocal microscopy indicated both cellular uptake of the fuorescent 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)497-510
Number of pages14
JournalInternational Journal of Nanomedicine
Volume7
StatePublished - Feb 10 2012

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Keywords

  • BeWo cells
  • Model optimization
  • Nanoparticles
  • Nanotoxicology
  • Placenta
  • Transport

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Cite this

Cartwright, L., Poulsen, M. S., Nielsen, H. M., Pojana, G., Knudsen, L. E., Saunders, M., & Rytting, E. (2012). In vitro placental model optimization for nanoparticle transport studies. International Journal of Nanomedicine, 7, 497-510.