Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature

© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 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 c...

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Main Authors: Lee, Sharon Wei Ling, Campisi, Marco, Osaki, Tatsuya, Possenti, Luca, Mattu, Clara, Adriani, Giulia, Kamm, Roger Dale, Chiono, Valeria
Other Authors: Singapore-MIT Alliance in Research and Technology (SMART)
Format: Article
Language:English
Published: Wiley 2021
Online Access:https://hdl.handle.net/1721.1/135529
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author Lee, Sharon Wei Ling
Campisi, Marco
Osaki, Tatsuya
Possenti, Luca
Mattu, Clara
Adriani, Giulia
Kamm, Roger Dale
Chiono, Valeria
author2 Singapore-MIT Alliance in Research and Technology (SMART)
author_facet Singapore-MIT Alliance in Research and Technology (SMART)
Lee, Sharon Wei Ling
Campisi, Marco
Osaki, Tatsuya
Possenti, Luca
Mattu, Clara
Adriani, Giulia
Kamm, Roger Dale
Chiono, Valeria
author_sort Lee, Sharon Wei Ling
collection MIT
description © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 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.
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spelling mit-1721.1/1355292023-09-01T19:31:42Z Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature Lee, Sharon Wei Ling Campisi, Marco Osaki, Tatsuya Possenti, Luca Mattu, Clara Adriani, Giulia Kamm, Roger Dale Chiono, Valeria Singapore-MIT Alliance in Research and Technology (SMART) Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Department of Biological Engineering © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 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. 2021-10-27T20:23:51Z 2021-10-27T20:23:51Z 2020 2020-08-17T16:45:07Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135529 en 10.1002/ADHM.201901486 Advanced Healthcare Materials Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Wiley Wiley
spellingShingle Lee, Sharon Wei Ling
Campisi, Marco
Osaki, Tatsuya
Possenti, Luca
Mattu, Clara
Adriani, Giulia
Kamm, Roger Dale
Chiono, Valeria
Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
title Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
title_full Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
title_fullStr Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
title_full_unstemmed Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
title_short Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
title_sort modeling nanocarrier transport across a 3d in vitro human blood brain barrier microvasculature
url https://hdl.handle.net/1721.1/135529
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