Placental Drug Transport‐on‐a‐Chip: A Microengineered In Vitro Model of Transporter‐Mediated Drug Efflux in the Human Placental Barrier

Abstract

The current lack of knowledge about the effect of maternally administered drugs on the developing fetus is a major public health concern worldwide. The first critical step toward predicting the safety of medications in pregnancy is to screen drug compounds for their ability to cross the placenta. However, this type of preclinical study has been hampered by the limited capacity of existing in vitro and ex vivo models to mimic physiological drug transport across the maternal-fetal interface in the human placenta. Here the proof-of-principle for utilizing a microengineered model of the human placental barrier to simulate and investigate drug transfer from the maternal to the fetal circulation is demonstrated. Using the gestational diabetes drug glyburide as a model compound, it is shown that the microphysiological system is capable of reconstituting efflux transporter-mediated active transport function of the human placental barrier to limit fetal exposure to maternally administered drugs. The data provide evidence that the placenta-on-a-chip may serve as a new screening platform to enable more accurate prediction of drug transport in the human placenta.

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

“…OOC system contained multilayered cell culture chambers can reproduce tissue–tissue interfaces by coculture of distinct cell types in compartmentalized microenvironments. Semipermeable and porous membranes, such as polycarbonates and PDMS, served as cell culture substrate are commonly incorporated into microchannels of OOC device to model diverse tissue barriers, such as lung alveolar interface, blood‐brain barrier (BBB), intestine barrier, kidney glomerular‐capillary barrier, and placental barrier . The membranes can be treated with coating of ECM proteins on surface to support cell adhesion, whereas significantly differ from native ECM.…”

Engineering and monitoring cellular barrier models

“…For this purpose, a co-culture of human trophoblasts and foetal endothelial cells were plated on either side of the semipermeable membrane under flow conditions. The model reproduced the efflux transport of a gestational diabetes drug (i.e., glyburide), mostly by active transporters in trophoblast cells [ 104 ]. In vitro models that faithfully recapitulate transport functions of placental barrier are essential to predict the exposure of foetus to drug compounds that may compromise foetal development during pregnancy.…”

Maternally administered naltrexone and its major active metabolite 6β-naltrexol transport across the placental barrierin vitro

“…Previous studies have proven the validity of using placenta-on-a-chip for assessing and replicating different drug transport analysis while mimicking physiological function of human placenta in vitro. [15][16][17][18][19][20][21] Through our most recent study, we analyzed caffeine transport across our fabricated microchip, and proved the model to be compatible with withstanding xenobiotic exposure. 21 Therefore, since placentaon-a-chip has yet to be tested with opioid contact, our study provides the first appraisal examining NTX and 6β-naltrexol on an organ-on-a-chip.…”

“…This study's intended purpose was to evaluate opioid transport in our placenta-on-a-chip model, and this stage of testing is made possible through the system and foundation of the placenta-ona-chip, microfluidic device. [18][19][20][21] Microfluidic devices provide us with the ability to culture and manage cellular and subcellular environments within our microchip, maintain fixed compositions of our cell lines, and replicate fluid movement in parallel layers. 11,[22][23][24][25][26][27][28] Our microfluidic device (( Figure 1 (d)-(f-f)) was fabricated using standard lithography techniques.…”