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

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TitleFlow dynamics, binding and detachment of spherical carriers targeted to ICAM-1 on endothelial cells.
Publication TypeJournal Article
Year of Publication2009
AuthorsCalderon, AJ, Muzykantov, V, Muro, S, Eckmann, DM
JournalBiorheology
Volume46
Issue4
Pagination323-41
Date Published2009
ISSN1878-5034
KeywordsAntibodies, Monoclonal, Drug Carriers, Drug Delivery Systems, Endothelium, Vascular, Humans, Intercellular Adhesion Molecule-1
Abstract

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 mum beads coated with ICAM-1 monoclonal antibody (Ab) at 370, 1100 or 4100 Ab/microm2. 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/microm2, 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/microm2, as a consequence of decreased rolling velocity. Carrier binding was stable even under a high shear stress: carriers with 1100 and 4100 Ab/microm2 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.

DOI10.3233/BIR-2009-0544
Alternate JournalBiorheology
PubMed ID19721193
PubMed Central IDPMC2766098
Grant ListP01 HL079063 / HL / NHLBI NIH HHS / United States
R01 EB006818 / EB / NIBIB NIH HHS / United States
R01 EB006818-02 / EB / NIBIB NIH HHS / United States
R01 HL087036 / HL / NHLBI NIH HHS / United States
R01 HL087036-04 / HL / NHLBI NIH HHS / United States
R01 HL087036-05 / HL / NHLBI NIH HHS / United States
R01 HL60230S1 / HL / NHLBI NIH HHS / United States
R21 HL085533 / HL / NHLBI NIH HHS / United States
T32 GM007612 / GM / NIGMS NIH HHS / United States