Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
Name
adhm.201901486.pdf
Description
Published version
Size
2.63 MB
Format
Adobe PDF
Checksum (MD5)
c858e8f8e8493b5448c96272b5c13512
Author(s)
Lee, Sharon Wei Ling
Campisi, Marco
Osaki, Tatsuya
Possenti, Luca
Mattu, Clara
Adriani, Giulia
Kamm, Roger Dale
Chiono, Valeria
Date Issued
2020
Journal
Advanced Healthcare Materials
Publisher
Wiley
Version
Final published version
Abstract
© 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.
MIT Department
Singapore-MIT Alliance in Research and Technology (SMART)
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/ADHM.201901486
