Modeling and Simulation of Circadian Rhythm and Spatiotemporal Dynamics of Ligand-coated Particle Flow in Targeted Drug Delivery Processes

Drug delivery via nanocarriers is a multi-faceted problem that aims at achieving maximum efficacy while minimizing off-target effects and enhancing therapeutic outcomes. Drug carrying nanoparticles are tethered with peptides or antibodies binding the surface of drug encapsulating nanoparticles. Computational Fluid Dynamics (CFD) methods can provide insights into effects of circadian rhythm on the drug-nanoparticle transport, distribution, and interactions with the vascular and interstitial environments. This paper presents an advanced fluid dynamics modeling method that is based on convective transport of viscous incompressible fluid (blood), coupled with a scalar advection diffusion equation for the formation of drug concentration gradients in the transport fluid domain, and buildup of concentration at the targeted site. The method is equipped with a experimentally calibrated particle-endothelial cell adhesion model, a friction model accounting for surface roughness of endothelial cell layer, and a dispersion model for particle transport in the boundary layer. Comparisons with carefully designed microfluidic experiments show predictive capability of the mathematical model for drug transport, adhesion, and retention at the target site.