CAREER: CONVECTIVE AND DIFFUSIVE TRANSPORT OF DRUG DELIVERY VEHICLES IN BLOOD FLOW IN MICROCIRCULATION

Project Details

Description

Bagchi0846293 This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Advances in high-performance computing have enabled the scientific community to progress toward the Direct Numerical Simulation of whole blood, at least in microcirculation. Despite the complexity of the problem, many research groups have succeeded in simulating the motion of multiple deformable blood cells in semi-dense suspension. Leveraging on this progress, this research addresses dispersion of drug-carriers in whole blood in presence of hundreds to thousands of deformable blood cells. Targeted drug delivery methods rely on carriers such as macromolecules and submicron particles to carry novel therapeutic agents precisely to disease location. They have shown great promise, for example, in cancer diagnosis and treatment. Once delivered, these carriers move through the bloodstream via convective and diffusive transport, and then bind to the diseased cells via adhesion molecules. This study will quantify the role of red blood cell dynamics (tumbling/tank-treading) in the dispersion of submicron particles under varying hemorheological conditions, compare the results with the classical Taylor-Aris theory of dispersion, and identify carrier size and hemorheological conditions for optimal dispersion. Direct Numerical Simulation (DNS) will be conducted on drug-carrier dispersion in whole blood represented as a semi-dense suspension of up to 1000 deformable blood cells flowing in a microvessel. Deformation and unsteady dynamics of individual blood cell will be resolved with high fidelity by appropriate mesocopic rheological models. The fluid/structure coupling will be done by an immersed boundary method. The simultaneous role of advection, diffusion, and biophysics of binding of a polymer on to a cell, and of a microsphere on to the vascular wall will be addressed. The DNS technique will be coupled with Lagrangian tracking of submicron particles, the bead-spring chain model for polymer stretching dynamics, and a coarse-grain model for molecular interaction during binding. The multidisciplinary research will impact prediction of complex fluid flows, multi-phase flows and fluid--solid interaction, and biology and disease (and potentially medicine). The computational and fluid dynamic research planned here will provide a theoretical basis for design of next-generation drug-carriers for normal and pathological blood with improved transport properties. An integrated educational plan includes encouraging, recruiting, and mentoring women students from K11-K12 in PI's research by coupling two till-date independent programs at Rutgers (Douglass Summer Institute for women, and Governor's School program for aspiring engineers). It also includes research experience for undergraduates, introduction of a cross-disciplinary course, and dissemination of results by organizing a mini-symposium on fluid mechanics of drug transport.
StatusFinished
Effective start/end date9/1/098/31/14

Funding

  • National Science Foundation (National Science Foundation (NSF))

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