Finally, we screened the BBB permeability for small molecules of clinical drugs by nano liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) using our hiPSC-derived BBB model. We selected ten drugs with known permeability properties for the evaluation. Notably, propranolol, caffeine, antipyrin, carbamazepine, and trazodone, which can all cross the BBB into the CNS by lipid-mediated free diffusion (indicated as CNS-positive drugs in Figure 6C), displayed high permeability coefficient values (Pe) (144.8 ± 26.3 to 879.4 ± 161.1 × 10−6 cm/s). In contrast, sulpiride, epinastine, cimetidine, quinidine, and prazosine, which have low BBB permeability as efflux transporter substrates (indicated as CNS-negative drugs in Figure 6C), showed low Pe (5.9 ± 2.6 to 53.2 ± 22.8 × 10−6 cm/s) (Figures 6B and 6C). These results indicated that our human iPSC-derived BBB model could be used to predict the permeability of developmental drugs.
