Predicting the size-dependent tissue accumulation of agents released from vascular targeted nanoconstructs

Vascular targeted nanoparticles have been developed for the delivery of therapeutic and imaging agents in cancer and cardiovascular diseases. However, at authors' knowledge, a comprehensive systematic analysis on their delivery efficiency is still missing. Here, a computational model is developed to predict the vesselwall accumulation of agents released from vascular targeted nanoconstructs. The transport problem for the released agent is solved using a finite volume scheme in terms of three governing parameters: the local wall shear rate S, ranging from 10 to 200 s^-1; the wall filtration velocity V_f , varying from 10^-9 to 10^-7 m/s; and the agent diffusion coefficient D, ranging from 10^-12 to 10 ^-9 m²/s. It is shown that the percentage of released agent adsorbing on the vessel walls in the vicinity of the vascular targeted nanoconstructs reduces with an increase in shear rate S, and with a decrease in filtration velocity V_f and agent diffusivity D. In particular, in tumor microvessels, characterized by lower shear rates (S = 10 s^-1) and higher filtration velocities (V_f = 10^-7 m/s), an agent with a diffusivity D = 10^-12 m²/s (i.e. a 50nm particle) is predicted to deposit on the vessel wall up to 30 % of the total released dose. Differently, drug molecules, exhibiting a smaller size and much higher diffusion coefficient (D = 10^-9 m²/s), are predicted to accumulate up to 70 %. In healthy vessels, characterized by higher S and lower V_f , the largest majority of the released agent is redistributed directly in the circulation. These data suggest that drug molecules and small nanoparticles only can be efficiently released from vascular targeted nanoconstructs towards the diseased vessel walls and tissue.