Fig. 3
Metabolic barrier function of the human BBB Chip. P-gp activities measured in the BBB Chip (a) versus BBB Transwells (b) that were pretreated with verapamil to inhibit the P-gp activity in the presence or absence of the P-gp substrates, rhodamine 123, DiOC2, or citalopram. c BBB efflux pump substrate selectivity and functionality measured in the BBB Chips using rhodamine 123 as a substrate of P-gp and MRP1 (left); DiOC2 as a substrate of P-gp and BCRP (middle); and doxorubicin interacting with P-gp (right) with or without addition of efflux transporter inhibitors (verapamil for P-gp, MK 571 for MRPs, and Ko143 for BCRP). Ratio of Papp indicates fold changes in the apparent permeability (Papp) of molecules resulting from chemical modulation of specific efflux pump activity. Data are presented as means ± SE, N = 2 for the chip experiments for rhodamine 123, DiOC2, and citalopram, as well as N = 3 for the BBB Transwell experiments and BBB chip experiments for Doxorubicin. The statistical analysis is two-way ANOVA with Tukey’s multiple comparisons test; *P < 0.05; **P < 0.001; ***P < 0.0001
