2020
DOI: 10.1002/adhm.201901486
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Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature

Abstract: Polymer nanoparticles (NPs), due to their small size and surface functionalization potential have demonstrated effective drug transport across the blood–brain–barrier (BBB). Currently, the lack of in vitro BBB models that closely recapitulate complex human brain microenvironments contributes to high failure rates of neuropharmaceutical clinical trials. In this work, a previously established microfluidic 3D in vitro human BBB model, formed by the self‐assembly of human‐induced pluripotent stem cell‐derived endo… Show more

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Cited by 68 publications
(102 citation statements)
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“…Several groups have made progress in this area by exposing iBMECs to hypoxia [19], modifying extracellular matrix composition and stiffness [62], or by optimizing hydrogel scaffolds and fluid flow parameters that allow for maintenance of barrier properties for up to 3 weeks [63]. Many of the BBB-chip platforms developed and optimized recently are now being used to investigate drug permeabilities [19,31,64,65], neurodegenerative disease [31,43,66], and other functional aspects of the BBB [33,60,61,67].…”
Section: Ipsc-derived Microfluidic Chip Models Of the Bbbmentioning
confidence: 99%
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“…Several groups have made progress in this area by exposing iBMECs to hypoxia [19], modifying extracellular matrix composition and stiffness [62], or by optimizing hydrogel scaffolds and fluid flow parameters that allow for maintenance of barrier properties for up to 3 weeks [63]. Many of the BBB-chip platforms developed and optimized recently are now being used to investigate drug permeabilities [19,31,64,65], neurodegenerative disease [31,43,66], and other functional aspects of the BBB [33,60,61,67].…”
Section: Ipsc-derived Microfluidic Chip Models Of the Bbbmentioning
confidence: 99%
“…The species-specific differences in transporter expression highlighted earlier [2][3][4][5][6] underscores the importance of using human-based models for testing these types of novel delivery mechanisms. Lastly, other alternative drug delivery strategies being explored using iPSC-derived BBB models are polymer nanoparticles [65] and perfusion of hyperosmolar agents like mannitol to temporarily open the BBB and permit the diffusion of non-permeable therapeutics into the CNS [19,61,67]. The development of iPSC-derived BBB models has significantly enhanced the ability to perform human-relevant in vitro drug screens and will likely continue to aid in the discovery and development of new therapeutics and CNS drug delivery methods.…”
Section: Drug Transport and Deliverymentioning
confidence: 99%
“…In vivo BBB properties are partially mimicked, with higher TEER (~ 450-1300 Ω cm 2 ), lower permeability coefficients and better transporter expression (e.g. GLUT-1, P-gp, MRP, BCRP) than BEC monolayers due to close interaction with perivascular cells [113,115,[118][119][120][121][122]. These models, particularly triple co-culture models, are based on the ability of astrocytes and pericytes, to induce BBB properties [119,123].…”
Section: Overview Of Bbb In Vitro Modelsmentioning
confidence: 99%
“…In vitro BBB models have been reported using primary PCs along with other human induced pluripotent stem cell (hiPSC)-derived cells (in particular BMECs). [31][32][33][34][35][36] In one study, human fetal brain astrocytes and PCs were cocultured with hiPSC-BMECs and neural progenitor cells to model the BBB. 37 Upregulated BBB genes ABCB1, SLC1A1, SLC2A1 (i.e., GLUT-1), and OCLN (the gene encoding Occludin) were observed.…”
Section: The Role Of Brain Pcs In the Blood-brain Barriermentioning
confidence: 99%