Dynamic Factors Controlling Targeting Nanocarriers to Vascular Endothelium

Endothelium lining the luminal surface of blood vessels is the key target and barrier for vascular drug delivery. Nanocarriers coated with antibodies or affinity peptides that bind specifically to endothelial surface determinants provide targeted delivery of therapeutic cargoes to these cells. Endothelial targeting consists of several phases including circulation in the bloodstream, anchoring on the endothelial surface and, in some cases, intracellular uptake and trafficking of the internalized materials. Dynamic parameters of the vasculature including the blood hydrodynamics as well as surface density, accessibility, membrane mobility and clustering of target determinants modulate these phases of the targeting, especially anchoring to endothelium. Further, such controlled parameters of design of drug nanocarriers such as affinity, surface density and epitope specificity of targeting antibodies, carrier size and shape also modulate endothelial targeting and resultant sub-cellular addressing. This article reviews experimental and computational approaches for analysis of factors modulating targeting nanocarriers to the endothelial cells.