In vitro placental model optimization for nanoparticle transport studies

TY - JOUR

T1 - In vitro placental model optimization for nanoparticle transport studies

AU - Cartwright, Laura

AU - Poulsen, Marie Sønnegaard

AU - Nielsen, Hanne Mørck

AU - Pojana, Giulio

AU - Knudsen, Lisbeth E.

AU - Saunders, Margaret

AU - Rytting, Erik

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Cell Line, Tumor

KW - Cell Survival

KW - Choriocarcinoma

KW - Female

KW - Fluorescent Dyes

KW - Humans

KW - Membrane Proteins

KW - Nanoparticles

KW - Particle Size

KW - Permeability

KW - Phosphoproteins

KW - Placenta

KW - Polycarboxylate Cement

KW - Polyesters

KW - Porosity

KW - Pregnancy

KW - Reproducibility of Results

KW - Transcytosis

KW - Uterine Neoplasms

KW - Zonula Occludens-1 Protein

U2 - 10.2147/IJN.S26601

DO - 10.2147/IJN.S26601

M3 - Journal article

C2 - 22334780

SN - 1176-9114

VL - 7

SP - 497

EP - 510

JO - International Journal of Nanomedicine (Print)

JF - International Journal of Nanomedicine (Print)

ER -