- DDS targeting to endothelium lining vasculature evolving as an efficient, specific and multifaceted drug delivery paradigm
- Coupling drugs to blood cells, in particular RBC and WBC, cardinally alters pharmacokinetics and effect of drugs
- Blood cells can transport drugs to endothelial cells in selected areas of the vascular system
- These approaches enable unprecedented degree of precision and efficacy of delivery and action of drugs in lungs, brain and other organs, targets of therapeutic interventions
Realization of magnificent potential of biologicals requires targeted delivery to the desirable sub-cellular compartments in the cells of interest. To achieve this goal, we as hundreds of other labs devise drug delivery systems (DDS), artificial - liposomes and nanoparticles, or natural such as proteins, cells and cell fragments. The intravascular targets include endothelial cells, lining the blood vessels, blood cells and components of the reticuloendothelial system (RES), all directly accessible to blood. In order to shift the uptake of DDSs circulating in the vascular system from high-capacity capturing by RES, we and others employ ligands of the epitopes that specifically exposed to blood from endothelial cells in the vascular areas of interest. The roster of such epitopes includes cell adhesion molecules (e.g., PECAM, ICAM, VCAM) and other endothelial markers. Liposomes. LNPs, fusions and other CAM-targeted carriers and DDS offer improved localization and effect. DDS featuring dual affinity to endothelial cells and red blood cells (RBCs) bind to RBCs, circulate on the surface of RBCs and transfer to endothelial cells expressing secondary binding sites (RBC hitchhiking). RBC carriers may also change other parameters of DDS pharmacokinetics (PK) and targeting. We will discuss examples of DDSs with solo avidity to endothelium or RBCs, as well as DDS with dual avidity to the vascular target cells. These approaches enable unprecedented degree of precision and efficacy of delivery and action of drugs in lungs, brain and other organs, targets of therapeutic interventions.
Vladimir Muzykantov, MD, PhD, Professor of Pharmacology and Medicine Vice-Chair, Department of Pharmacology Director, Center for Targeted Therapeutics & Translational Nanomedicine, University of Pennsylvania The Perelman School of Medicine
