We develop a multiscale hydrodynamic transport model of transvascular drug delivery from nanocarrier “encapsulated droplets” or “vesicles”. Appreciable drug loss occurs from the microcarrier from the point of injection to the point of target tissue binding. The interplay between mechanical forces due to blood flow, receptor-ligand interactions, and physicochemical processes such as membrane dynamics as well as intra-membrane (lateral) diffusion determine the timescale of nanocarrier arrest on the target cell. This is a major determinant of drug delivery efficacy into endothelial cells. Tunable properties such as nanocarrier size, receptor and ligand surface density, contact surface area between the vehicle and target cells, and drug permeability and diffusivity through the membranes influence drug transport.
We predict conditions of microcarrier arrest on target endothelial cells by modeling near wall vesicle motion and drug transport, including binding mechanics, receptor/ligand diffusion, membrane deformation, and post-attachment convection-diffusion transport interactions to evaluate drug permeation into endothelial cells. We then determine optimal parameters for the nanocarrier design to achieve/control specified drug transport into the endothelia by exploring a range of tunable properties (or parameter space) – nanocarrier size, ligand/receptor concentration, receptor-ligand interaction, drug permeability out of the nanocarrier, lateral diffusion coefficients of ligands on nanocarrier membrane, and membrane stiffness - in the simulations.
To capture the nanocarrier trajectory amidst receptor mediated adhesion to endothelial cells, a multiscale algorithm bridging a kinetic Monte Carlo approach with deterministic continuum equations was developed. Together with collaborative experiments this integrated multiscale modeling and experimental approach is employed in the optimal engineering design of drug delivery systems for targeted disease treatment.