Vladimir Muzykantov

Title : Targeting nanomedicine to the vascular endothelium

Abstract:

Endothelial cells lining the vascular lumen represent an important therapeutic target in many dangerous maladies. Some of them have no effective pharmacotherapy, at least in part due to inadequate drug delivery to intended site of action. Coupling drugs and carriers with specific affinity ligands enables targeted endothelial drug delivery in animal studies. Combining in vivo and in vitro approaches provide the insights into the complex mechanistic aspects of endothelial targeting. Briefly, endothelial drug targeting, uptake, traffic and effects are governed, among other design parameters, by: i) ligand nature, affinity and conjugation; ii) carrier’s size, shape and plasticity; iii) supramolecular configuration of assembled targeted carrier (valence, ligand’s steric freedom). Biological factors modulating targeting include carrier’s interactions with molecules and cells en route, target accessibility, functional consequences of anchoring to specific epitope and its location. Pathological factors alter perfusion, vascular permeability, epitope accessibility and endothelial status and carrier uptake. Permutations of design and biological factors yield complex and somewhat difficult to reduce to practice, yet multifaceted and diversified paradigms for vascular drug delivery and targeting. In animal models of human diseases, endothelial targeting of antioxidant, anti-thrombotic and anti-inflammatory agents provides beneficial effects unrivaled by untargeted counterparts. This approach may provide tangible therapeutic benefits in conditions including acute lung injury, ischemia-reperfusion and sepsis. Current studies aim to define mechanisms and utility of “endothelial nanomedicine”.

Audience take away:
• They will be able to use this in their research and educational activities in the fields of nanomedicine and drug delivery
• The ideas and results shown in the presentation will guide their research and educational activities, support their own design of drug delivery systems, help solve practical and translational problems, provide examples and facilitate the interpretation of their own and literature data.  

Biography:

Vladimir Muzykantov (MD from First Moscow Medical School, 1980 and Ph.D. in Biochemistry from Russian National Cardiology Research Center, 1985), joined PENN in 1993 and in 2010 became a Professor and Vice-Chair of the Department of Systems Pharmacology and Translational Therapeutics. He established and since 2010 directs the Center for Targeted Therapeutics and Translational Nanomedicine. He published >200 papers and edited a book “Biomedical Aspects of Drug Targeting” (Kluwer, 2003). Honors include Established Investigator (1996) and Bugher Stroke (2000) Awards from the American Heart Association, the Keynote and Chairing forums including Transatlantic Airway Conference on Targeting Molecular Signatures in Lungs (Luzerne, 2009), Gordon Conference on Drug Carriers (2012) and HLBI Division of Lung Diseases Workshop “Precision Therapeutics Delivery for Lung Diseases” (2014), Annual Italian Society of Biochemistry and Molecular Biology Conference (2015). His research focuses on drug delivery by red blood cells and endothelial targeting for treatment inflammation, thrombosis and ischemia.