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.
Supplementary data
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The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID, NICHD, OD or the NIH.
Acknowledgements
A portion of this work was presented at the 40th Annual Meeting & Exposition of the Controlled Release Society (CRS) and subsequently highlighted in the 31st volume of the CRS Newsletter.
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.