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 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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BibTeX
@article{lee2026modeling,
title = {{Modeling Nanocarrier Transport across a 3D In Vitro Human Blood-Brain–Barrier Microvasculature}},
author = {Sharon Wei Ling Lee and Marco Campisi and Tatsuya Osaki and Luca Possenti and Clara Mattu and Giulia Adriani and Roger Dale Kamm and Valeria Chiono},
journal = {Advanced Healthcare Materials},
year = {2026},
month = oct,
doi = {10.1002/adhm.201901486},
url = {https://hal.science/hal-05776433v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Modeling Nanocarrier Transport across a 3D In Vitro Human Blood-Brain–Barrier Microvasculature
AU - Sharon Wei Ling Lee
AU - Marco Campisi
AU - Tatsuya Osaki
AU - Luca Possenti
AU - Clara Mattu
AU - Giulia Adriani
AU - Roger Dale Kamm
AU - Valeria Chiono
PY - 2026
DA - 2026/10/03
JO - Advanced Healthcare Materials
DO - 10.1002/adhm.201901486
UR - https://hal.science/hal-05776433v1
AB - 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.
SN - 2192-2640
SN - 2192-2659
ER -