In VitroAssays for Assessing BBB Permeability

In VitroBlood–Brain Barrier Permeability and Cytotoxicity of an Atorvastatin-Loaded Nanoformulation Against Glioblastoma in 2D and 3D Models

“…This includes permeation through the BBB after, e.g., parenteral administration . Several sophisticated in vitro BBB models were developed in recent years to resemble the situation in vivo . − Apart from the cellular barrier, the in vivo situation is also complicated by flow, which has been taken into consideration by some recent models . One promising approach involves models based on human induced-pluripotent stem cells (hiPSCs)-derived BBB endothelial cells. , Using such a hiPSC-derived model, physiological characteristics like high transendothelial electrical resistances (TEER) up to 2500 Ω·cm 2 , distinct upregulation of typical BBB genes as well as the formation of an in vivo -like tight junction network could be achieved .…”

“…87 Several sophisticated in vitro BBB models were developed in recent years to resemble the situation in vivo. [88][89][90] Apart from the cellular barrier, the in vivo the situation is also complicated by flow, which has been taken into consideration by some recent models. 91 One promising approach are models based on human induced pluripotent stem cells (hiPSCs) derived BBB endothelial cells.…”

Optimization of a Pyrimidinone Series for Selective Inhibition of Ca2+/Calmodulin-Stimulated Adenylyl Cyclase 1 Activity for the Treatment of Chronic Pain

“…Based on these calculations, analogues 16 , 20 , and 39 all are predicted to be CNS-inactive with values of −2 for each, while 38 has a predicted value of 0, indicating at least partial CNS activity. Alternatively, Madin–Darby canine kidney (MDCK) cells have been shown to be a viable surrogate to assess for BBB permeability. , This is captured in the QPPMDCK apparent permeability ( P app ) metric where a predicted P app > 500 nm/s is desired for CNS activity. Analogues 16 , 20 , and 39 all had QPPMDCK P app values around 140 nm/s, which would support the reduced CNS score, while 38 was predicted to have a value of 632 nm/s (Table ), indicating that it was the most likely of the cohort to reach the desired site of action.…”