Flow dynamics,binding and detachment of spherical carriers targeted to ICAM-1 on endothelial cells

Vascular drug delivery by administration of carriers targeted to endothelial surface determinants, such as intercellular adhesion molecule (ICAM-1), holds considerable promise to improve disease treatment. As a model to define elusive factors controlling the interplay between carrier motion in the bloodstream and its interactions with molecular targets in the endothelial wall, we used 1 μm beads coated with ICAM-1 monoclonal antibody (Ab) at 370, 1100 or 4100 Ab/μm². Carriers were perfused at two shear rates over resting or activated endothelial cells, expressing minimum vs. maximum ICAM-1 levels, to determine carrier rolling, binding and detachment. Even at 0.1 Pa and 4100 Ab/μm², carriers attached only to activated cells (21 fold increase over resting cells), ideal for specific drug targeting to sites of pathology. Binding was increased by raising the Ab surface density on the carrier, e.g., 59.4±11.1% increase for carriers having 4100 vs. 1100 Ab/μm², as a consequence of decreased rolling velocity. Carrier binding was stable even under a high shear stress: carriers with 1100 and 4100 Ab/μm² withstand shear stress over 3 Pa without detaching from the cells. This is further supported by theoretical modeling. These results will guide vascular targeting of drug carriers via rational design of experimentally tunable parameters.