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. 2015;6(12):1325-34.
doi: 10.4155/tde.15.79.

Transport of digoxin-loaded polymeric nanoparticles across BeWo cells, an in vitro model of human placental trophoblast

Norah A Albekairi  1 , Sanaalarab Al-Enazy  1 , Shariq Ali  1 , Erik Rytting  1   2
Affiliations

Transport of digoxin-loaded polymeric nanoparticles across BeWo cells, an in vitro model of human placental trophoblast

Norah A Albekairi et al. Ther Deliv. 2015.

Abstract

Background: Fetal arrhythmias can lead to fetal congestive heart failure and hydrops fetalis. Digoxin (the first-line treatment) has low transplacental permeability and high risk of maternal side effects. Biodegradable digoxin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles may increase digoxin transport across BeWo b30 cell monolayers (an in vitro model of trophoblast in human placenta) by reducing the drug's interaction with P-gp. Results/methodology: The nanoparticles showed high encapsulation efficiency and sustained release over 48 h. Transport studies revealed significantly increased permeability across BeWo cell layers of digoxin-loaded nanoparticles when compared with free digoxin. P-gp inhibition also increased the permeability of digoxin, but not digoxin-loaded nanoparticles.

Conclusion: This represents a novel treatment strategy for fetal cardiovascular disease which may improve maternal and fetal outcomes.

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Conflict of interest statement

Financial & competing interests disclosure Support from the Saudi Cultural Mission is gratefully acknowledged. This work was also supported in part by a research career development award (K12HD052023: Building Interdisciplinary Research Careers in Women's Health Program, BIRCWH) from the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the Office of the Director (OD), NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. In vitro drug release of digoxin from polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles (RGPd50105, 10% drug loading) over 48 h under sink conditions at 37°C in phosphate-buffered saline.
The inset shows the fit of the data to the Higuchi equation (as described in the ‘Release study’ subsection). Error bars represent the standard deviation (n = 3). PLGA: Poly(lactic-co-glycolic acid).
<b>Figure 2.</b>
Figure 2.. Biocompatibility of blank polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles in BeWo cells at various concentrations after 4, 24 and 48 h of exposure, as assessed by the WST-1 colorimetric assay.
Triton X-100 was used as a negative control, and blank cell culture medium without nanoparticles was used as the positive control (set to 100% cell viability). The error bars represent the standard deviation (n = 6). PLGA: Poly(lactic-co-glycolic acid).
<b>Figure 3.</b>
Figure 3.. Apparent permeability (Pe) for the transport of free digoxin (white bar) and digoxin-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles (RGPd50105, 10% drug loading, black bar) across BeWo cell monolayers in the apical (maternal) to basolateral (fetal) direction at the 2-h time point.
The transport studies were carried out at 37°C under cell culture conditions with stirring. Pe was also determined for both formulations in the presence of 100 μM verapamil, a P-gp inhibitor. Asterisks indicate significant differences from the permeability of free digoxin (p < 0.05). There were no significant differences between the Pe values of the digoxin-loaded nanoparticles, free digoxin in the presence of verapamil (dark gray bar) or digoxin-loaded nanoparticles in the presence of verapamil (light gray bar). Error bars indicate standard deviation (n = 3). PLGA: Poly(lactic-co-glycolic acid).
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