A Hybrid Particle-Cell Model for Nanoparticle Targeted Delivery in Microcirculation

Abstract

Multifunctional nanomedicine holds considerable promise as the next generation of medicine that allows for targeted therapy with minimal toxicity. Most current theoretical studies considered nanoparticle (NP) suspensions in a Newtonian fluid without blood cells [1–3]. However, blood is a complex biological fluid composed of deformable cells, proteins, platelets, and plasma. For blood flow in capillary, arterioles and venules, the particulate nature of the blood need to be considered in the delivery process. Non-Newtonian effects such as the cell-free-layer and nanoparticle-cell interaction will largely influence both the dispersion and binding rates, thus impact targeted delivery efficacy. In this paper, a particle-cell hybrid model is developed to model NP transport, dispersion, and adhesion dynamics in blood suspension. The motion and deformation of red blood cell is captured through Immersed Finite Element method. The motions and adhesion of individual NPs are tracked through Brownian adhesion dynamics. A mapping and interaction potential function is introduced to consider the cell-particle collision. NP dispersion and binding coefficients are derived from the developed model under various rheology conditions. The influence of vascular flow rate, diameter, and particle size on NP distribution and delivery efficacy is characterized.