(596o) Effect of Poly(ethylene glycol) Spacers On the Vascular Targeting of Particles to Endothelium in Blood

Vascular targeting is an intriguing means for therapeutic treatment and diagnosis of cardiovascular diseases such as atherosclerosis.  To target diseased tissue particulate carriers are modified to contain antibodies or epitopes, such as anti-intercellular adhesion molecule-1 (aICAM-1) and Sialyl Lewis^a.  Along with targeting moieties, poly(ethylene glycol) spacers are used to improve circulation time by reducing protein adsorption on the surface of particles.  Though the use of poly(ethylene glycol) to reduce protein adsorption is well studied, little work has been done on examining the effect of poly(ethylene glycol) on adhesion dynamics; specifically in human blood flow.  Here we exam the influence of different molecular weight poly(ethylene glycol) spacers on particle adhesion dynamics to inflamed human endothelial cells in blood. Polystyrene nano/microspheres were grafted with poly(ethylene glycol) spacers of different lengths and densities to serve as a linker between particle surface and targeting ligand – anti-ICAM-1 or Sialyl Lewis^a.  Targeted particles in human blood were then perfused over a monolayer of IL-1β stimulated human umbilical chord endothelial cells using a parallel plate flow chamber at shear rates of 200 s^‑1, 500 s^‑1, and 1000 s^‑1. Poly(ethylene glycol) spacers were shown to improve binding flux of antibody-coated microspheres to activated cells but had no effect on the binding flux of Sialyl Lewis^a –coated microspheres and.the dynamics appear to be a function of PEG surface conformation and blood shear rate