Modeling Nanocarrier Transport across a 3D In Vitro Human Blood-Brain-Barrier Microvasculature.
human blood-brain-barrier
in vitro testing platforms
microfluidic devices
polymer nanoparticles
self-organized microvasculatures
Journal
Advanced healthcare materials
ISSN: 2192-2659
Titre abrégé: Adv Healthc Mater
Pays: Germany
ID NLM: 101581613
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
20
10
2019
revised:
16
12
2019
pubmed:
4
3
2020
medline:
15
5
2021
entrez:
4
3
2020
Statut:
ppublish
Résumé
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 endothelial cells, primary brain pericytes, and astrocytes in triculture within a 3D fibrin hydrogel is exploited to quantify polymer NP permeability, as a function of size and surface chemistry. Microvasculature are perfused with commercially available 100-400 nm fluorescent polystyrene (PS) NPs, and newly synthesized 100 nm rhodamine-labeled polyurethane (PU) NPs. Confocal images are taken at different timepoints and computationally analyzed to quantify fluorescence intensity inside/outside the microvasculature, to determine NP spatial distribution and permeability in 3D. Results show similar permeability of PS and PU NPs, which increases after surface-functionalization with brain-associated ligand holo-transferrin. Compared to conventional transwell models, the method enables rapid analysis of NP permeability in a physiologically relevant human BBB set-up. Therefore, this work demonstrates a new methodology to preclinically assess NP ability to cross the human BBB.
Identifiants
pubmed: 32125776
doi: 10.1002/adhm.201901486
pmc: PMC7486802
mid: NIHMS1575469
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1901486Subventions
Organisme : NINDS NIH HHS
ID : R21 NS105027
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214381
Pays : United States
Informations de copyright
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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