An engineered microfluidic blood‐brain barrier model to evaluate the anti‐metastatic activity of β‐boswellic acid

Abstract Background The development of anti‐cancer drugs with the ability to inhibit brain metastasis through the blood‐brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models. Main Methods In this study, the Geltrex‐based Transwell and microfluidic BBB models were applied to screen the effect of β‐boswellic acid (β‐BA) on the metastasis of MDA‐MB‐231 cells through the BBB in static and dynamic conditions, respectively. Major Results The toxicity assay revealed that β‐BA deteriorates MDA‐MB‐231 cells, while β‐BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans‐endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with β‐BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of β‐BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. β‐BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that β‐BA‐mediated metastasis inhibition was significantly higher than that mediated by Cis. Conclusions and Implications In summary, the current study proved the anti‐metastatic potential of β‐BA in both static and dynamic BBB models.