Transport of Maternally Administered Pharmaceutical Agents Across the Placental Barrier In Vitro

Date
2022-04-05
Authors
Pemathilaka, Rajeendra L.
Alimoradi, Nima
Reynolds, David E.
Hashemi, Nicole
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American Chemical Society
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Mechanical Engineering
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Biomedical Sciences
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Ames Laboratory
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Bioeconomy Institute
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Mechanical EngineeringBiomedical SciencesAmes LaboratoryBioeconomy Institute
Abstract
To understand the transport of pharmaceutical agents and their effects on developing fetus, we have created a placental microsystem that mimics structural phenotypes and physiological characteristic of a placental barrier. We have shown the formation of a continuous network of epithelial adherens junctions and endothelial cell–cell junctions confirming the integrity of the placental barrier. More importantly, the formation of elongated microvilli under dynamic flow condition is demonstrated. Fluid shear stress acts as a mechanical cue triggering the microvilli formation. Pharmaceutical agents were administered to the maternal channel, and the concentration of pharmaceutical agents in fetal channel for coculture and control models were evaluated. In fetal channel, the coculture model exhibited about 2.5 and 2.2% of the maternal initial concentration for naltrexone and 6β-naltrexol, respectively. In acellular model, fetal channel showed about 10.5 and 10.3% of the maternal initial concentration for naltrexone and 6β-naltrexol, respectively. Gene expressions of epithelial cells after direct administration of naltrexone and 6β-naltrexol to the maternal channel and endothelial cells after exposure due to transport through placental barrier are also reported.
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This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in ACS Applied Bio Materials, copyright © 2022 The Authors. To access the final edited and published work see DOI: 10.1021/acsabm.2c00121. Posted with permission.
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