Late-stage placental barrier model for transport studies of prescription drugs during pregnancy†
Abstract
Throughout pregnancy, the placental barrier is crucial for fetal development, evolving continuously to meet the growing nutritional demands of the fetus. Although the placenta has the capacity to selectively filter compounds, harmful xenobiotic substances from the maternal blood can sometimes cross over into the fetal circulation. This drives the development of in vitro placental barrier models in the context of drug transport studies. In this work, we adapted our lab's previous placental barrier model to transplacental drug transport by transitioning from self-assembled vasculature to a simplified straight tubular vasculature to improve throughput and consistency. We then closely examined the angiogenic cytokine secretion and crosstalk between trophoblasts and endothelial cells. Furthermore, we validated this model for drug barrier studies by assessing the permeability of three model therapeutic agents: paclitaxel, vancomycin, and IgG. Drug permeabilities were shown to be drug type, concentration, and size dependent, similar to what has previously been reported. The presented model offers a promising tool for enhancing drug safety assessments in pregnant women, ensuring both maternal well-being and fetal health.