Simulating Local Nanoparticulate Drug Delivery Systems

Simulating Local Nanoparticulate Drug Delivery Systems in Patient-specific Coronary Arteries to Treat Atherosclerosis Contributors from ICES, The University of Texas at Austin: Shaolie Hossain and Thomas J.R. Hughes Visualization by Karla Vega, Texas Advanced Computing Center, The University of Texas at Austin. Abstract: A vast majority of heart attacks occur when there is a sudden rupture in the atherosclerotic plaque built-up in the coronary arteries, exposing its prothrombotic core materials (e.g., lipids) to the blood flow, forming blood clots that can cause blockage of the arterial lumen. The diseased arteries can be treated with drugs delivered locally (intravascularly injected) to these rupture-prone plaques termed "vulnerable plaques". In designing these local drug delivery devices, important issues regarding drug distribution and targeting need to be addressed to ensure device design optimization for maximum therapeutic efficacy. Therefore, a computational tool-set was developed to support the design and analysis of a catheter-based local drug delivery system that uses nanoparticles as drug carriers to treat vulnerable plaques and diffuse atherosclerosis. Simulations were run on a 3D patient-specific multilayered diseased coronary artery segment obtained directly from CT-imaging data and the effect of artery wall and plaque inhomogeneity on drug distribution was analyzed. The figure depicts a cross-section of the artery taken right through the vulnerable plaque with a large lipid core and a thin fibrous cap that is formed near the coronary artery bifurcation region. Results show the drug (in red) accumulating in the target region, that is, the lipid core of the vulnerable plaque, which is highly encouraging from a therapeutic point of view. The tool is now poised to be used in medical device industry to address important design questions such as, "given a particular desired drug-tissue concentration in a specific patient, what would be the optimum location, particle release mechanism, drug release rate, drug properties, and so forth, for maximum efficacy?"