CAREER: Defining the interplay between hemodynamics and shape/size in particle localization to the vascular wall - an integrated in vitro and in vivo study

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This CAREER award will lead research in which a combination of in vitro and in vivo assays will used to systematically explore how shape and size dictates particle margination (localization and adhesion) dynamics in complex blood flow typical of medium and large blood vessels (M/LBVs). To date, limited attention has been given to how the interplay between particle shape/size and hemodynamics that prescribe the margination of vascular-targeted carriers to the vascular wall. While its effect may be minimal in capillaries, hemodynamics must be an important consideration in the design of drug carriers for application in M/LBVs involved in several human diseases. For example, atherosclerosis, the leading cause of death among adults in the US, is a multistage disease of M/LBVs (arteries). Improvements to the current treatments for atherosclerosis, statins therapy or bypass surgery, are necessary since, for instance, acute coronary events can still occur in 50-70% of patients on statins. Targeting drugs to the vascular wall via inflammation associated with atherosclerosis could provide a more viable approach for treating this disease. Yet, nanospheres typically proposed as vascular-targeted carriers have recently been shown to not be effective in localizing to the wall in M/LBVs. Larger microspheres that have a hemodynamic advantage for binding, however, can cause occlusion in capillaries. One approach to addressing this issue is a paradigm shift away from the spherical shape. The PI hypothesizes that spheroids would better marginate to the valscular wall in M/LBVs due to their complex hemodynamic interactions. Thus, the PI will characterize the in vitro margination spheroids in complex blood flow, and determine their in vivo efficacy. Since the PI?s research activities are driven by core chemical engineering (ChE) principles, it allows for the integration of her research into ChE education at all levels. Thus, this CAREER proposal will link the PI?s research activities to her educational program by (i) using her research to show ChE sophomores in the material and energy balance course how the knowledge of core ChE principles can be pieced together to solve important health problems and (ii) exposing graduate students to new knowledge created from this CAREER award in her ?Drug Delivery and Targeting? graduate course, and (iii) providing mentored research opportunities to underrepresented minority (URM) women in engineering. The PI is also developing a novel ?each-one-teach-one? multi-year on-campus K-12 outreach program focused on boosting the undergraduate enrollment of students of all backgrounds in engineering, where a cohort of students from a local school district are exposed to ChE concepts via undergraduate class projects.