Placenta-on-a-chip: Response of neural cells to pharmaceutical agents transported across the placental barrier

Abstract

Striving for sustainable drug discovery, we have presented a proof-of-concept for studying the effects of pharmaceutical agents transported across the placental barrier on neural cells. The potential effects of pharmaceutical agents on fetus have made concerns about their use and require more studies to address these concerns. A placenta-on-a-chip model was fabricated and tested for transport of naltrexone (NTX) and its primary metabolite 6β-naltrexol. The NTX/6β-naltrexol transported from the maternal channel to the fetal channel was then collected from the fetal channel. To evaluate the behavior of neural cells following exposure to NTX and 6β-naltrexol, perfusate from the fetal channel was directed toward the cultured N27 neural cells. Neural cells exposed to the transported NTX/6β-naltrexol were then evaluated for gene expression and cell viability. Results showed significantly higher fold changes in IL-6 and TNF-α expression when exposed to NTX/6β-naltrexol. However, a lower fold change in IL-1β expression was observed, while it remained the same in sphingosine kinase (sphk)1. Also, cell viability with NTX/6β-naltrexol exposure was determined to be significantly lower (p < 0.001). This study has the potential to reveal the impact of pharmaceutical agents on the developing neural system of fetuses and their premature brains.