title: Effect of PEGylation on ligand-based targeting of drug carriers to the vascular wall in blood flow.
abstract: The blood vessel wall plays a prominent role in the development of many life-threatening diseases and as such is an attractive target for treatment. To target diseased tissue, particulate drug carriers often have their surfaces modified with antibodies or epitopes specific to vascular wall-expressed molecules, along with poly(ethylene glycol) (PEG) to improve carrier blood circulation time. However, little is known about the effect of poly(ethylene glycol) on carrier adhesion dynamics-specifically in blood flow. Here we examine the influence of different molecular weight PEG spacers on particle adhesion in blood flow. Anti-ICAM-1 or Sialyl Lewis(a) were grafted onto polystyrene 2 μm and 500 nm spheres via PEG spacers and perfused in blood over activated endothelial cells at physiological shear conditions. PEG spacers were shown to improve, reduce, or have no effect on the binding density of targeted-carriers depending on the PEG surface conformation, shear rate, and targeting moiety.
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Onyskiw
authors.forename: Omolola
authors.initials: O
authors.lastname: Eniola-Adefeso
mesh_terms: D000906:Antibodies / Q000737:chemistry; D018395:CA-19-9 Antigen; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D018056:Hemorheology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology; D054118:Nanospheres / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011137:Polystyrenes / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000906:Antibodies; D018395:CA-19-9 Antigen; D004337:Drug Carriers; D009844:Oligosaccharides; D011137:Polystyrenes; D018799:Intercellular Adhesion Molecule-1; D011092:Polyethylene Glycols