(93j) Effect of Dual Ligand Chemistry on Particle Adhesion to Inflamed Endothelium in Vivo

The expression of certain endothelial cell adhesion molecules (e.g. E-selectin, P-selectin) is increased at sites of inflammation. We recently demonstrated how this local upregulation of ECAMs can be exploited to target biodegradable drug carriers to inflamed endothelium. Particularly, we showed that biodegradable particles conjugated with either a ligand to P-selectin alone or a ligand to E-selectin alone exhibit enhanced adhesion in a murine model of inflammation. We sought to determine whether particles bearing dual ligands would exhibit augmented adhesion to inflamed endothelium as compared to particles bearing a single ligand. Preliminary data suggest that particles bearing ligands to both E-selectin and P-selectin exhibit at least 2 fold enhanced adhesion to inflamed endothelium as compared to particles bearing a ligand to E-selectin alone. We are currently investigating the underlying mechanism for the enhanced adhesion of dual ligand particles.