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Targeted delivery of therapeutics to endothelium Simone E; Ding BS; Muzykantov VCell Tissue Res 2009[Jan]; 335 (1): 283-300The endothelium is a target for therapeutic and diagnostic interventions in a plethora of human disease conditions including ischemia, inflammation, edema, oxidative stress, thrombosis and hemorrhage, and metabolic and oncological diseases. Unfortunately, drugs have no affinity to the endothelium, thereby limiting the localization, timing, specificity, safety, and effectiveness of therapeutic interventions. Molecular determinants on the surface of resting and pathologically altered endothelial cells, including cell adhesion molecules, peptidases, and receptors involved in endocytosis, can be used for drug delivery to the endothelial surface and into intracellular compartments. Drug delivery platforms such as protein conjugates, recombinant fusion constructs, targeted liposomes, and stealth polymer carriers have been designed to target drugs and imaging agents to these determinants. We review endothelial target determinants and drug delivery systems, describe parameters that control the binding of drug carriers to the endothelium, and provide examples of the endothelial targeting of therapeutic enzymes designed for the treatment of acute vascular disorders including ischemia, oxidative stress, inflammation, and thrombosis.|*Endothelium, Vascular/metabolism/physiology[MESH]|Animals[MESH]|Antigens, Differentiation/metabolism[MESH]|Drug Carriers/chemistry/*therapeutic use[MESH]|Edema/drug therapy/metabolism/pathology[MESH]|Hemorrhage/drug therapy/metabolism/pathology[MESH]|Humans[MESH]|Ischemia/*drug therapy/metabolism/pathology[MESH]|Metabolic Diseases/drug therapy/metabolism/pathology[MESH]|Neoplasms/drug therapy/metabolism/pathology[MESH]|Oxidative Stress/*drug effects[MESH]|Thrombosis/*drug therapy/metabolism/pathology[MESH] |
