Electroporation of Brain Endothelial Cells on Chip toward Permeabilizing the Blood-Brain Barrier. Bonakdar, M., Wasson, E. M., Lee, Y. W., & Davalos, R. V. Biophys J, 110(2):503-513, 2016. 1542-0086 Bonakdar, Mohammad Wasson, Elisa M Lee, Yong W Davalos, Rafael V R21 CA173092/CA/NCI NIH HHS/United States 5R21 CA173092-01/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States 2016/01/21 Biophys J. 2016 Jan 19;110(2):503-513. doi: 10.1016/j.bpj.2015.11.3517.doi abstract bibtex The blood-brain barrier, mainly composed of brain microvascular endothelial cells, poses an obstacle to drug delivery to the brain. Controlled permeabilization of the constituent brain endothelial cells can result in overcoming this barrier and increasing transcellular transport across it. Electroporation is a biophysical phenomenon that has shown potential in permeabilizing and overcoming this barrier. In this study we developed a microengineered in vitro model to characterize the permeabilization of adhered brain endothelial cells to large molecules in response to applied pulsed electric fields. We found the distribution of affected cells by reversible and irreversible electroporation, and quantified the uptaken amount of naturally impermeable molecules into the cells as a result of applied pulse magnitude and number of pulses. We achieved 81 ± 1.7% (N = 6) electroporated cells with 17 ± 8% (N = 5) cell death using an electric-field magnitude of ∼580 V/cm and 10 pulses. Our results provide the proper range for applied electric-field intensity and number of pulses for safe permeabilization without significantly compromising cell viability. Our results demonstrate that it is possible to permeabilize the endothelial cells of the BBB in a controlled manner, therefore lending to the feasibility of using pulsed electric fields to increase drug transport across the BBB through the transcellular pathway.
@article{RN179,
author = {Bonakdar, M. and Wasson, E. M. and Lee, Y. W. and Davalos, R. V.},
title = {Electroporation of Brain Endothelial Cells on Chip toward Permeabilizing the Blood-Brain Barrier},
journal = {Biophys J},
volume = {110},
number = {2},
pages = {503-513},
note = {1542-0086
Bonakdar, Mohammad
Wasson, Elisa M
Lee, Yong W
Davalos, Rafael V
R21 CA173092/CA/NCI NIH HHS/United States
5R21 CA173092-01/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
United States
2016/01/21
Biophys J. 2016 Jan 19;110(2):503-513. doi: 10.1016/j.bpj.2015.11.3517.},
abstract = {The blood-brain barrier, mainly composed of brain microvascular endothelial cells, poses an obstacle to drug delivery to the brain. Controlled permeabilization of the constituent brain endothelial cells can result in overcoming this barrier and increasing transcellular transport across it. Electroporation is a biophysical phenomenon that has shown potential in permeabilizing and overcoming this barrier. In this study we developed a microengineered in vitro model to characterize the permeabilization of adhered brain endothelial cells to large molecules in response to applied pulsed electric fields. We found the distribution of affected cells by reversible and irreversible electroporation, and quantified the uptaken amount of naturally impermeable molecules into the cells as a result of applied pulse magnitude and number of pulses. We achieved 81 ± 1.7% (N = 6) electroporated cells with 17 ± 8% (N = 5) cell death using an electric-field magnitude of ∼580 V/cm and 10 pulses. Our results provide the proper range for applied electric-field intensity and number of pulses for safe permeabilization without significantly compromising cell viability. Our results demonstrate that it is possible to permeabilize the endothelial cells of the BBB in a controlled manner, therefore lending to the feasibility of using pulsed electric fields to increase drug transport across the BBB through the transcellular pathway.},
keywords = {Animals
Blood-Brain Barrier/*metabolism
*Capillary Permeability
Cell Line
Electroporation/instrumentation/*methods
Endothelial Cells/*metabolism
Mice
Microfluidics/instrumentation/methods},
ISSN = {0006-3495 (Print)
0006-3495},
DOI = {10.1016/j.bpj.2015.11.3517},
year = {2016},
type = {Journal Article}
}
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Our results provide the proper range for applied electric-field intensity and number of pulses for safe permeabilization without significantly compromising cell viability. Our results demonstrate that it is possible to permeabilize the endothelial cells of the BBB in a controlled manner, therefore lending to the feasibility of using pulsed electric fields to increase drug transport across the BBB through the transcellular pathway.","keywords":"Animals Blood-Brain Barrier/*metabolism *Capillary Permeability Cell Line Electroporation/instrumentation/*methods Endothelial Cells/*metabolism Mice Microfluidics/instrumentation/methods","issn":"0006-3495 (Print) 0006-3495","doi":"10.1016/j.bpj.2015.11.3517","year":"2016","bibtex":"@article{RN179,\n author = {Bonakdar, M. and Wasson, E. M. and Lee, Y. W. and Davalos, R. V.},\n title = {Electroporation of Brain Endothelial Cells on Chip toward Permeabilizing the Blood-Brain Barrier},\n journal = {Biophys J},\n volume = {110},\n number = {2},\n pages = {503-513},\n note = {1542-0086\nBonakdar, Mohammad\nWasson, Elisa M\nLee, Yong W\nDavalos, Rafael V\nR21 CA173092/CA/NCI NIH HHS/United States\n5R21 CA173092-01/CA/NCI NIH HHS/United States\nJournal Article\nResearch Support, N.I.H., Extramural\nResearch Support, Non-U.S. Gov't\nUnited States\n2016/01/21\nBiophys J. 2016 Jan 19;110(2):503-513. doi: 10.1016/j.bpj.2015.11.3517.},\n abstract = {The blood-brain barrier, mainly composed of brain microvascular endothelial cells, poses an obstacle to drug delivery to the brain. Controlled permeabilization of the constituent brain endothelial cells can result in overcoming this barrier and increasing transcellular transport across it. Electroporation is a biophysical phenomenon that has shown potential in permeabilizing and overcoming this barrier. In this study we developed a microengineered in vitro model to characterize the permeabilization of adhered brain endothelial cells to large molecules in response to applied pulsed electric fields. We found the distribution of affected cells by reversible and irreversible electroporation, and quantified the uptaken amount of naturally impermeable molecules into the cells as a result of applied pulse magnitude and number of pulses. We achieved 81 ± 1.7% (N = 6) electroporated cells with 17 ± 8% (N = 5) cell death using an electric-field magnitude of ∼580 V/cm and 10 pulses. Our results provide the proper range for applied electric-field intensity and number of pulses for safe permeabilization without significantly compromising cell viability. 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