Targeted nanocarriers for delivery of drugs to the vascular endothelium

摘要

Delivery and effects of most drugs remain suboptimal, since they have no natural affinity to their intended therapeutic targets. Further, biotherapeutics including enzymes not only require protection against inactivation but typically need specific sub-cellular addressing that is not naturally attainable. Endothelial cells lining the vascular lumen represent an important therapeutic target in vascular, pulmonary and other disease conditions. Delivery of therapeutics to endothelial cells can be optimized using nanocarriers targeted to anchor molecules expressed on the endothelial luminal surface. In particular, cell adhesion molecules represent attractive targets for endothelial drug delivery in the context of inflammation and oxidative stress. We have devised and tested in animal models a series of nanocarriers for endothelial delivery of antioxidants, showing superior protective features vs non-targeted counterparts. These nanocarriers offer a spectrum of controllable features that help to optimize parameters of drug delivery: pharmacokinetics, circulation in blood, binding to selected endothelial cell phenotypes, intracellular addressing and duration of the therapeutic effects.