(548b) Engineering Particle Shape to Evade Interactions with the Mononuclear Phagocyte System

A major limitation in the use of synthetic carriers designed for drug delivery and diagnostic applications is their rapid clearance from the body by mononuclear phagocyte system (MPS), which is one of body's innate modes of defense against invading pathogens and other non-indigenous particulate matter. Novel design principles with respect to particle shape and flexibility have been proposed recently which have added a new dimension to evade the MPS. Elucidating the interactions of particles with the MPS is extremely important in designing carriers that can perform the delivery tasks efficiently. Opsonization of injected particles by antibodies in circulation, attachment of opsonized particles to the macrophages and subsequent internalization by phagocytosis form the important steps in the clearance of particles by MPS. The importance of opsonization and particle geometry in exclusive internalization studies has already been reported in literature. Here, we illustrate the importance of particle geometry in attachment of opsonized particles using a particle toolbox consisting of different sizes (0.5μm, 1μm and 3μm) and shapes (spheres, rods and oblate ellipsoids). Particles were coated with mouse IgG to mimic opsonization. Particles were incubated with RAW 264.7 mouse macrophages at 4oC to avoid internalization and study only the attachment to macrophages. In the current study, we observed that opsonized particles showed significantly higher attachment to macrophages as compared with non-opsonized particles. Moreover, in case of smaller particles (0.5μm and 1μm), particles with higher contact surface area (elongated particles) exhibited higher attachment tendency. For larger particles (3μm), the attachment was limited by the exposed surface area of the macrophage since it is comparable to the particle surface area. Hence, spheres which exhibit the least contact surface area were attached to the highest extent. A combined effect of attachment and internalization, representative of the entire particle population interacting with the macrophages would give us a thorough insight into whether elongated particles can circulate longer in comparison to spherical counter parts. Thus, the importance of geometry of opsonized particles in attachment to macrophages has been illustrated which will contribute to the design rules for long circulating carrier fabrication for efficient delivery of drugs.