Understanding particle margination in blood flow - A step toward optimized drug delivery systems

Abstract

Targeted delivery of drugs and imaging agents is very promising to develop new strategies for the treatment of various diseases such as cancer. For an efficient targeted adhesion, the particles have to migrate toward the walls in blood flow - a process referred to as margination. Due to a huge diversity of available carriers, a good understanding of their margination properties in blood flow depending on various flow conditions and particle properties is required. We employ a particle-based mesoscopic hydrodynamic simulation approach to investigate the margination of different carriers for a wide range of hematocrits (volume fraction of red blood cells) and flow rates. Our results show that margination strongly depends on the thickness of the available free space close to the wall, the so-called red blood cell-free layer (RBC-FL), in comparison to the carrier size. The carriers with a few micrometers in size are comparable with the RBC-FL thickness and marginate better than their sub-micrometer counterparts. Deformable carriers, in general, show worse margination properties than rigid particles. Particle margination is also found to be most pronounced in small channels with a characteristic size comparable to blood capillaries. Finally, different margination mechanisms are discussed.

Keywords: Drug carriers; Mesoscopic simulation; Micro- and nano-particles; Particle and cell migration; Red blood cells.