Abstract
Understanding drug transport across the placental barrier is important for assessing the potential fetal drug toxicity and birth defect risks. Current in vivo and in vitro models have structural and functional limitations in evaluating placental drug transfer and toxicity. Microphysiological systems (MPSs) offer more accurate and relevant physiological models of human tissues and organs on a miniature scale for drug development and toxicology testing. MPSs for the placental barrier have been recently explored to study placental drug transfer. We utilized a multilayered hydrogel membrane-based microphysiological model composed of human placental epithelial and endothelial cells to replicate the key structure and function of the human placental barrier. A macroscale human placental barrier model was created using a transwell to compare the results with the microphysiological model. Placental barrier models were characterized by assessing monolayer formation, intercellular junctions, barrier permeability, and their structural integrity. Three small molecule drugs (glyburide, rifaximin, and caffeine) that are prescribed or taken during pregnancy were studied for their placental transfer. The results showed that all three drugs crossed the placental barrier, with transfer rates in the order: glyburide (molecular weight, MW = 494Da) < rifaximin (MW = 785.9Da) < caffeine (MW = 194.19Da). Using non-compartmental analysis, we estimated human pharmacokinetic characteristics based on in vitro data from both MPS and transwell models. While further research is needed, our findings suggest that MPS holds potential as an in vitro tool for studying placental drug transfer and predicting fetal exposure, offering insights into pharmacokinetics.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.