Predicting the vascular adhesion of deformable drug carriers in narrow capillaries traversed by blood cells

In vascular targeted therapies, blood-borne carriers should realize sustained drug release from the luminal side towards the diseased tissue. In this context, such carriers are required to firmly adhere to the vessel walls for a sufficient period of time while resisting force perturbations induced by the blood flow and circulating cells. Here, a hybrid computational model, combining a Lattice Boltzmann (LBM) and Immersed Boundary Methods (IBM), is proposed for predicting the strength of adhesion of particles in narrow capillaries (7.5μm) traversed by blood cells. While flowing down the capillary, globular and biconcave deformable cells (7μm) encounter 2μm discoidal particles, adhering to the vessel walls. Particles present aspect ratios ranging from 0.25 to 1.0 and a mechanical stiffness varying from rigid (Ca = 0) to soft (Ca = 10−3). Cell-particle interactions are quantitatively predicted over time via three independent parameters: the cell membrane stretching δp; the cell-to-particle distance r, and the number of engaged ligand-receptor bonds NL. Under physiological flow conditions (Re = 10−2), rigid particles are detached and displaced away from the wall by blood cells. This is associated with a significant cell membrane stretching (up to 10%) and rapid breaking of molecular bonds (t umax/H <1). Differently, soft particles deform their shape as cells pass by, thus reducing force perturbations and extending the life of molecular bonds. Yet, only the thinnest deformable particles (2 ×0.5μm) firmly adhere to the walls under all tested configurations. These results suggest that low aspect ratio deformable particles can establish long-lived adhesive interactions with capillary walls, enabling de facto vascular targeted therapies.