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

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 6ß-naltrexol, respectively. In acellular model, fetal channel showed about 10.5 and 10.3% of the maternal initial concentration for naltrexone and 6ß-naltrexol, respectively. Gene expressions of epithelial cells after direct administration of naltrexone and 6ß-naltrexol to the maternal channel and endothelial cells after exposure due to transport through placental barrier are also reported.

Behavior of Neural Cells Post Manufacturing and After Prolonged Encapsulation within Conductive Graphene-Laden Alginate Microfibers.

Engineering conductive 3D cell scaffoldings offer advantages toward the creation of physiologically relevant platforms with integrated real-time sensing capabilities. Dopaminergic neural cells are encapsulated into graphene-laden alginate microfibers using a microfluidic approach, which is unmatched for creating highly-tunable microfibers. Incorporating graphene increases the conductivity of the alginate microfibers by 148%, creating a similar conductivity to native brain tissue. The cell encapsulation procedure has an efficiency of 50%, and of those cells, ≈30% remain for the entire 6-day observation period. To understand how the microfluidic encapsulation affects cell genetics, tyrosine hydroxylase, tubulin beta 3 class 3, interleukin 1 beta, and tumor necrosis factor alfa are analyzed primarily with real-time reverse transcription-quantitative polymerase chain reaction and secondarily with enzyme-linked immunosorbent assay, immediately after manufacturing, after encapsulation in polymer matrix for 6 days, and after encapsulation in the graphene-polymer composite for 6 days. Preliminary data shows that the manufacturing process and combination with alginate matrix affect the expression of the studied genes immediately after manufacturing. In addition, the introduction of graphene further changes gene expressions. Long-term encapsulation of neural cells in alginate and 6-day exposure to graphene also leads to changes in gene expressions.

Placenta-on-a-Chip: In Vitro Study of Caffeine Transport across Placental Barrier Using Liquid Chromatography Mass Spectrometry.

Due to the particular structure and functionality of the placenta, most current human placenta drug testing methods are limited to animal models, conventional cell testing, and cohort/controlled testing. Previous studies have produced inconsistent results due to physiological differences between humans and animals and limited availability of human and/or animal models for controlled testing. To overcome these challenges, a placenta-on-a-chip system is developed for studying the exchange of substances to and from the placenta. Caffeine transport across the placental barrier is studied because caffeine is a xenobiotic widely consumed on a daily basis. Since a fetus does not carry the enzymes that inactivate caffeine, when it crosses a placental barrier, high caffeine intake may harm the fetus, so it is important to quantify the rate of caffeine transport across the placenta. In this study, a caffeine concentration of 0.25 mg mL-1 is introduced into the maternal channel, and the resulting changes are observed over a span of 7.5 h. A steady caffeine concentration of 0.1513 mg mL-1 is reached on the maternal side after 6.5 h, and a 0.0033 mg mL-1 concentration on the fetal side is achieved after 5 h.

Drug transport across the human placenta: review of placenta-on-a-chip and previous approaches.

In the past few decades, the placenta became a very controversial topic that has had many researchers and pharmacists discussing the significance of the effects of pharmaceutical drug intake and how it is a possible leading cause towards birth defects. The creation of an in vitro microengineered model of the placenta can be used to replicate the interactions between the mother and fetus, specifically pharmaceutical drug intake reactions. As the field of nanotechnology significantly continues growing, nanotechnology will become more apparent in the study of medicine and other scientific disciplines, specifically microengineering applications. This review is based on past and current research that compares the feasibility and testing of the placenta-on-a-chip microengineered model to the previous and underdeveloped in vivo and ex vivo approaches. The testing of the practicality and effectiveness of the in vitro, in vivo and ex vivo models requires the experimentation of prominent pharmaceutical drugs that most mothers consume during pregnancy. In this case, these drugs need to be studied and tested more often. However, there are challenges associated with the in vitro, in vivo and ex vivo processes when developing a practical placental model, which are discussed in further detail.