Numerical simulation of Nanoparticle delivery in microcirculation

Multifunctional nanomedicine holds considerable promise as the next generation of medicine that allows for targeted therapy with minimal toxicity. To evaluate the delivery efficiency of Nanoparticles (NPs), it is important to study their transport, binding and distribution in blood flow. For blood flow in capillaries, arterioles and venules, the particulate nature of the blood and physiological conditions needs to be considered in the delivery process. The existence of the cell-free-layer, NP-cell interaction, particle shape and vessel geometry will largely influence the dispersion, binding rates and distribution, thus impact targeted delivery efficacy. In this thesis, a particle-cell hybrid model is developed to model NP transport, dispersion, and binding dynamics in blood suspension. The motion and deformation of red blood cells is captured through the Immersed Finite Element Method. The motion and adhesion of individual NPs are tracked through Brownian adhesion dynamics. The influence of red blood cells, vascular flow rate, particle size, shape and vessel geometry effect on NP distribution and delivery efficacy is characterized. With red blood cells, a non-uniform NP distribution profile with higher particle concentration near the vessel wall is observed, which leads to over 50% higher particle binding rate compared to the case without red blood cell. The tumbling motion of red blood cells in the core region of the capillary is found to enhance NP dispersion, and dispersion rate increases with shear rate. The simulation results also indicate that NPs with smaller size and rod shape have higher binding rates. The binding dynamics of rod-shaped NPs is found to be dependent on their initial contact points and orientations to the wall. Moreover, it is found that Peclet number plays an important role in determining the fraction of NPs deposited in the branched region and the straight section. Simulation results also indicate that NP binding rate decreases with increased shear rate. Dynamic NP re-distribution from low to high shear rates is observed due to the non-uniform shear stress distribution over the branched channel. Results from this study contribute to the fundamental understanding and knowledge on how the particulate nature of blood, size, shape and vessel geometry influences NP delivery and distribution, which will provide mechanistic insights on the nanomedicine design for targeted drug delivery applications.