Figure 9.

Penetration of selected PP compounds across in vitro BBB model membrane: (A) Schematic representation of a triple-coculture model of the BBB, which consists of astrocytes, pericytes and epithelial cells cultured on 24-well transwell membranes with 3 μm pores. Trans-endothelial electric resistance (TEER) was measured using a EVOM² meter with a STX3 electrode (World Precision Instruments). (B) BBB permeability (P) for the selected compounds was calculated using P = V_A⋅C_A/(t⋅S⋅C_L) equation⁵¹ and normalized by TEER coefficient. Data represent average values from 2 independent experiments in triplicates (n = 6) with standard deviation SD. * indicates values significantly different from fenofibrate (negative control), and caffeine was used as positive control. Panel C: HR68 (PP21) tissue concentration evaluated in Foxn1 nude mice bearing intracranial glioblastoma (GBM12). Mice were treated intraperitoneally (ip) with HR68 diluted in 20% cyclodextrin at 15 mg/kg/day and the levels of HR68 in the blood, heart, liver, kidney, spleen, lung, brain and in brain tumor (BT), were evaluated by HPLC, as we previously reported^21,24. Data represent average values with standard deviation (n = 3). Please note that average glioblastoma IC50 for HR68 is 1.17 µM, and we detected 3.7 ± 0.5 µM of HR68 in the brain tumor tissue.