2018
DOI: 10.1016/j.jconrel.2018.01.024
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In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain

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Cited by 48 publications
(34 citation statements)
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“…In addition, the BBB constructs of Transwell systems are still 2D planar models with less resemblance to the 3D microscale capillary architecture of the BBB in vivo [63]. With the advancement of different microscale technologies, numerous microdevices have been developed to provide in vivo-like microenvironments and 3D culture models [63]. Such microfluidic based models have many advantages over existing in vitro static models, including shear stress stimulation.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, the BBB constructs of Transwell systems are still 2D planar models with less resemblance to the 3D microscale capillary architecture of the BBB in vivo [63]. With the advancement of different microscale technologies, numerous microdevices have been developed to provide in vivo-like microenvironments and 3D culture models [63]. Such microfluidic based models have many advantages over existing in vitro static models, including shear stress stimulation.…”
Section: Discussionmentioning
confidence: 99%
“…These recently described advanced microfluidic models provided 3D structure, cell-cell interaction, and the exposure to shear stress that resulted in better barrier function compared to conventional transwell models [70][71][72][73]. Moreover, they have characterized the dynamic permeability of drugs/markers, which make them more like in vivo permeability studies compared to the Transwell system [70,72,74]. However, there are still challenges ahead for developing in vitro model of BBB due to different designs of models and quantitative protocols.…”
Section: Importance Of Permeability Studies In Advanced Bbb-on-chip Mmentioning
confidence: 99%
“…Some models have attempted to visualize transport across the BBB in real time; 40,41 however, the shear stresses applied in these experiments (3.8 × 10 −3 to 0.15 dyn/cm 2 ) are often orders of magnitude lower than what are considered physiologically relevant within the brain microvasculature (1-30 dyn/cm 2 ). 24,[42][43][44] Maintaining the culture under higher shear stress for prolonged periods of time in a microfluidic environment poses a significant challenge. 45 This limitation is especially significant given that previous reports indicate low shear stresses may be insufficient to induce the proper morphological and biochemical changes.…”
Section: Introductionmentioning
confidence: 99%