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In vitro model for predicting the access and distribution of drugs in the brain using hCMEC/D3 cells


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Título :
In vitro model for predicting the access and distribution of drugs in the brain using hCMEC/D3 cells
Autor :
Sánchez-Dengra, Bárbara  
González Álvarez, Isabel
Sousa, Flavia
Bermejo, Marival
González Álvarez, Marta
Sarmento, Bruno  
Editor :
Elsevier
Departamento:
Departamentos de la UMH::Ingeniería
Fecha de publicación:
2021-04-08
URI :
https://hdl.handle.net/11000/34653
Resumen :
The BBB is a protective entity that prevents external substances from reaching the CNS but it also hinders the delivery of drugs into the brain when they are needed. The main objective of this work was to improve a previously proposed in vitro cell-based model by using a more physiological cell line (hCMEC/D3) to predict the main pharmacokinetic parameters that describe the access and distribution of drugs in the CNS: Kpuu,brain, fu, plasma, fu,brain and Vu,brain. The hCMEC/D3 permeability of seven drugs was studied in transwell systems under different conditions (standard, modified with albumin and modified with brain homogenate). From the permeability coefficients of those experiments, the parameters mentioned above were calculated and four linear IVIVCs were established. The best ones were those that relate the in vitro and in vivo Vu,brain and fu,brain (r2 = 0.961 and r2 =0.940) which represent the binding rate of a substance to the brain tissue, evidencing the importance of using brain homogenate to mimic brain tissue when an in vitro brain permeability assay is done. This methodology could be a high-throughput screening tool in drug development to select the CNS promising drugs in three different in vitro BBB models (hCMEC/D3, MDCK and MDCK-MDR1).
Palabras clave/Materias:
Blood brain barrier (BBB)
IVIVC
Unbound fraction (fu)
Distribution volume in brain (Vu,brain)
Plasma brain partition coefficient (Kpuu,brain)
Área de conocimiento :
CDU: Ciencias aplicadas: Ingeniería. Tecnología
Tipo de documento :
info:eu-repo/semantics/article
Derechos de acceso:
info:eu-repo/semantics/closedAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
DOI :
https://doi.org/10.1016/j.ejpb.2021.04.002
Aparece en las colecciones:
Artículos Ingeniería



Creative Commons La licencia se describe como: Atribución-NonComercial-NoDerivada 4.0 Internacional.