Abstract
Permeation is one of the most evaluated parameters using preclinical in vitro blood-brain barrier models, as it has long been considered to be one of the major factors influencing central nervous system drug delivery. Blood-brain barrier permeability can be defined as the speed at which a compound crosses the brain endothelial cell barrier and is employed to assess barrier tightness, which is a crucial feature of brain capillaries in vivo. In addition, it is used to assess brain drug penetration. We review traditionally used methods to assess blood-brain barrier permeability in vitro and summarize often neglected in vivo (e.g., plasma protein and brain tissue binding) or in vitro (e.g., culture insert materials or methodology) factors that influence this property. These factors are crucial to consider when performing BBB permeability assessments, and especially when comparing permeability data obtained from different models, since model diversification significantly complicates inter-study comparisons. Finally, measuring transendothelial electrical resistance can be used to describe blood-brain barrier tightness; however, several parameters should be considered while comparing these measurements to the blood-brain barrier permeability to paracellular markers.
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Acknowledgments
The authors (ARSM, MH, MD, MC) were supported by the European Commission within the framework of a Marie Sklodowska-Curie Innovative Training Network: BtRAIN – European Brain Barriers Training Network (H2020-MSCA-ITN-2015, n°675619). MD and ARSM were supported by the M-ERA.NET2 nanoPD project financed by the National Research, Development and Innovation Office, Hungary (OTKA NNE 129617), and the Hungarian Academy of Sciences. ARSM received an ÚNKP-20-4-SZTE-593 fellowship. FW was supported by the János Bolyai Research Fellowship of the Hungarian Academy of Sciences; the National Research, Development and Innovation Office, Hungary (OTKA PD-128480); the ÚNKP-19-SZTE42 and ÚNKP-20-5-SZTE-672, Bolyai + Scholarship New National Excellence Program of the Ministry for Innovation and Technology. WN was supported by the SET foundation project 060. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 807015. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA (WN).
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Santa-Maria, A.R. et al. (2020). Transport Studies Using Blood-Brain Barrier In Vitro Models: A Critical Review and Guidelines. In: Cader, Z., Neuhaus, W. (eds) Physiology, Pharmacology and Pathology of the Blood-Brain Barrier. Handbook of Experimental Pharmacology, vol 273. Springer, Cham. https://doi.org/10.1007/164_2020_394
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