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 6[Formula: see text]-naltrexol. The NTX/6[Formula: see text]-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 6[Formula: see text]-naltrexol, perfusate from the fetal channel was directed toward the cultured N27 neural cells. Neural cells exposed to the transported NTX/6[Formula: see text]-naltrexol were then evaluated for gene expression and cell viability. Results showed significantly higher fold changes in IL-6 and TNF-[Formula: see text] expression when exposed to NTX/6[Formula: see text]-naltrexol. However, a lower fold change in IL-1[Formula: see text] expression was observed, while it remained the same in sphingosine kinase (sphk)1. Also, cell viability with NTX/6[Formula: see text]-naltrexol exposure was determined to be significantly lower ([Formula: see text]). This study has the potential to reveal the impact of pharmaceutical agents on the developing neural system of fetuses and their premature brains.