Organ-on-a-Chip Approach for Accelerating Blood–Brain Barrier Nanoshuttle Discovery

Organ-on-a-chip, which recapitulates
the dynamics of in
vivo vasculature, has emerged as a promising platform for
studying organ-specific vascular beds. However, its practical advantages
in identifying vascular-targeted drug delivery systems (DDS) over
traditional in vitro models remain underexplored.
This study demonstrates the reliability and efficacy of the organ-on-a-chip
in screening efficient DDS by comparing its performance with that
of a conventional transwell, both designed to simulate the blood–brain
barrier (BBB). The BBB nanoshuttles discovered through BBB Chip-based
screening demonstrated superior functionality in vivo compared to those identified using transwell methods. This enhanced
effectiveness is attributed to the BBB Chip’s accurate replication
of the structure and dynamics of the endothelial glycocalyx, a crucial
protective layer within blood vessels, especially under shear stress.
This capability of the BBB Chip has enabled the identification of
molecular shuttles that efficiently exploit the endothelial glycocalyx,
thereby enhancing transendothelial transport efficacy. Our findings
suggest that organ-on-a-chip technology holds considerable promise
for advancing research in vascular-targeted DDS due to its accurate
simulation of molecular transport within endothelial systems.