Vascular pathologies such as inflammation, thromboses, atherosclerosis, and malignancies require accurate targeting of imaging and therapeutic agents for effective diagnosis and treatment. This proposal aims to develop a novel biomimetic platform to evaluate drug-carrying nanoparticle transport and biodistribution in a vascular bed. The nanoparticle biodistribution is largely influenced by local vascular geometry and flow. There is currently no simple tool to predict particle biodistribution in a complex vascular network. The primary goal of this work is to predict nanomedicine transport and distribution in a pulmonary vascular bed through complementary microfluidic tests and computational modeling. The proposed research will advance understanding of the mechanism of nanocarrier transport in the bloodstream, and will provide a systematic tool to achieve targeted dosage and optimal distribution for specific vascular geometries and hemodynamic conditions. The objectives of the proposed work are: (1) Develop a microfluidic evaluation platform consisting of a vascular morphology-based biomimetic microfluidic channel network, target receptor and endothelium coating for determination of nanoparticle binding distribution and efficacy;(2) Apply a multiscale model to simulate nanoparticle distribution in microfluidic channels and in a 3D lung vasculature, and compare the modeled distribution with experimental results and existing in vivo data. The major advantage of the proposed technique, compared to current flow-chamber and in vivo studies, is that we relate molecular binding of drug nanoparticles to macroscopic biodistribution using fast evaluation of multiple parameters and minimal sample volume. This methodology will enable accurate and efficient estimation of nanoparticle biodistribution in patient-specific vascular geometries.
This research project responds to the request of the Academic Research Enhancement Award (AREA) program to stimulate biomedical research activities at our university, which as a whole has not been a major recipient of NIH support. We propose to develop an innovative and integrated microfluidic and computational platform for high throughput nanomedicine distribution testing and to answer key questions on the characteristics of nanoparticle targeted delivery in a complex vascular bed. Successful execution of the project will benefit the treatment and imaging of vascular diseases by predicting vascular level details of drug carrier distribution.
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