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

Pemathilaka, Rajeendra L.; Alimoradi, Nima; Reynolds, David E.; Hashemi, Nicole

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

File

2022-HashemiNicole-TransportMaternally.pdf (1.91 MB)

Date

2022-04-05

Authors

Pemathilaka, Rajeendra L.

Alimoradi, Nima

Reynolds, David E.

Hashemi, Nicole

Publisher

American Chemical Society

Authors

Person

Hashemi, Nicole

Associate Professor

Organizational Units

Organizational Unit

Mechanical Engineering

The Department of Mechanical Engineering at Iowa State University is where innovation thrives and the impossible is made possible. This is where your passion for problem-solving and hands-on learning can make a real difference in our world. Whether you’re helping improve the environment, creating safer automobiles, or advancing medical technologies, and athletic performance, the Department of Mechanical Engineering gives you the tools and talent to blaze your own trail to an amazing career.

Organizational Unit

Biomedical Sciences

The Department of Biomedical Sciences aims to provide knowledge of anatomy and physiology in order to understand the mechanisms and treatment of animal diseases. Additionally, it seeks to teach the understanding of drug-action for rational drug-therapy, as well as toxicology, pharmacodynamics, and clinical drug administration.

History
The Department of Biomedical Sciences was formed in 1999 as a merger of the Department of Veterinary Anatomy and the Department of Veterinary Physiology and Pharmacology.

Dates of Existence
1999–present

Related Units

College of Veterinary Medicine (parent college)
Department of Veterinary Anatomy (predecessor, 1997)
Department of Veterinary Physiology and Pharmacology (predecessor, 1997)

Organizational Unit

Ames National Laboratory

Ames National Laboratory is a government-owned, contractor-operated national laboratory of the U.S. Department of Energy (DOE), operated by and located on the campus of Iowa State University in Ames, Iowa.

For more than 70 years, the Ames National Laboratory has successfully partnered with Iowa State University, and is unique among the 17 DOE laboratories in that it is physically located on the campus of a major research university. Many of the scientists and administrators at the Laboratory also hold faculty positions at the University and the Laboratory has access to both undergraduate and graduate student talent.

Organizational Unit

Bioeconomy Institute

The Bioeconomy Institute at Iowa State University leads the nation and world in establishing the bioeconomy, where society obtains renewable fuel, energy, chemicals, and materials from agricultural sources. The institute seeks to advance the use of biorenewable resources for the production of fuels, energy, chemicals, and materials. The Institute will assure Iowa’s prominence in the revolution that is changing the way society obtains its essential sources of energy and carbon. This revolution will dramatically reduce our dependence on petroleum. Instead of fossil sources of carbon and energy, the bioeconomy will use biomass (including lignocellulose, starches, oils and proteins) as a renewable resource to sustain economic growth and prosperity. Agriculture will supply renewable energy and carbon to the bioeconomy while engineering will transform these resources into transportation fuels, commodity chemicals, and electric power. This transformation, however, must be done in a manner that meets our present needs without compromising those of future generations.

Department

Mechanical EngineeringBiomedical SciencesAmes National 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.

Comments

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.