Shear targeted drug delivery to stenotic blood vessels |
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| Affiliation: | 1. Experimental Physics I, Institute of Physics, University of Augsburg, Universitätsstr. 1, 86159 Augsburg, Germany;2. Physiology, Institute of Theoretical Medicine, University of Augsburg, Universitätsstraße 2, 86159 Augsburg, Germany;3. Center for NanoScience (CeNS), Ludwig-Maximilians-Universität Munich, 80799 Munich, Germany;1. Departments of Biomedical Engineering;2. Departments of Neonatology, Carmel Medical Center and the Ruth and Bruce Rappaport Faculty of Medicine;1. Biomaterials Science Center, University of Basel, Allschwil, Switzerland;2. Nanomedicine Research and Education Center, Semmelweis University, Budapest, Hungary;3. Department of Chemistry, University of Fribourg, Fribourg, Switzerland;4. Cardiology Division, University Hospitals of Geneva, Geneva, Switzerland |
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| Abstract: | In this review we focus on shear targeted drug delivery as a novel strategy to selectively deliver drugs to sites of vascular obstruction. We review the physics of stenotic (abnormally narrowed) blood vessels, while focusing mainly on the hemodynamics and transport phenomena at these sites. We then discuss how the local abnormal levels of shear stress, which can mechanically activate platelets, can be leveraged for localized drug delivery. We describe the development of Shear Activated Nano-particle Aggregates (SA-NPAs) that are designed to release and localize their nanoparticle drug carriers at sites of vascular stenosis. We present results in a variety of in vivo models, demonstrating the superiority of SA-NPAs carrying a thrombolytic drug compared to conventional treatment with the free drug. We also describe, shear-stress sensitive lenticular liposomes, which also show selective release under stenotic flow conditions. We then discuss limitations of both technologies, challenges in this new field and potential future applications. Altogether, we believe that mechano-sensitive therapeutics may offer a potential new approach for treatment of cardiovascular diseases. |
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| Keywords: | Shear stress Drug delivery Stenosis Hemodynamics |
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