title: Targeting delivery of drugs in the vascular system.
abstract: Delivery and effects of therapeutics remain suboptimal. Most drugs do not have affinity to their targets. Biotherapeutics including enzymes and genetic materials require specific sub-cellular addressing not attainable naturally. Endothelium, lining the luminal surface of blood vessels, represents a key therapeutic target in many diseases. Studies in cell culture and animal models revealed that targeted delivery of therapeutics to, into and across endothelium can be achieved using carriers targeted to specific molecules expressed on the surface of the endothelial cells. For example, cell adhesion molecules represent attractive targets for drug delivery. Rational design of the drug delivery systems (e.g., selection of optimal geometry and affinity to specific epitopes) provides an unprecedented level of control of such parameters of drug delivery as pharmacokinetics, circulation in blood, binding to selected endothelial cell phenotypes, anchoring on cell surface or internalization into the endothelium, subsequent intracellular addressing and duration of the effects. We discusse here key aspects of design of endothelium-targeted drug delivery systems with potential for translation into the clinical domain.
authors.affiliation: Professor of Pharmacology, University of Pennsylvania, 3620 Hamilton Walk, 1 John Morgan Building, Philadelphia, PA 19104-6068, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Muzykantov
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, 5115 Plant Sciences Building, College Park, MD 20742.
authors.forename: Silvia
authors.initials: S
authors.lastname: Muro
keywords: Vascular endothelium; cell adhesion molecules; drug carriers; drug targeting; stealth nanocarriers