(102d) Exploring Deformable Hydrogel Microparticles Carriers for Vascular-Targeted Drug Delivery Applications

Vascular-targeted carriers (VTCs) are drug-loaded nano- and microparticles designed to accumulate at the vascular wall of diseased tissue for therapeutic purposes. However, a significant challenge is the rapid removal of VTCs from circulation by RES organs and clearance by phagocytic leukocytes. As a result, current research focuses on designing VTCs to avoid phagocytic uptake and extend circulation times. One important design parameter that recently gained attention is the particle modulus and its impact on VTC effectiveness. While previous studies have largely accepted that softer particles are better suited to evade macrophage and monocyte clearance and have longer circulation times, these findings have been generalized to all leukocytes. This work investigates the effects of particle elastic modulus on phagocytosis by primary human neutrophils using particles composed of either polyethylene glycol (PEG) or a rigid polystyrene (PS) control, with a focus on the interplay between modulus, surface charge, and material selection. This study finds cellular differences between different phagocytes, including neutrophils, macrophages, and monocytes, that can arise when examining the context of VTC phagocytosis. Specifically, administering deformable particles to neutrophils enhances phagocytosis, highlighting the need for further characterization of VTC design parameters with respect to neutrophils. These results have important implications for VTC design for human use, especially in vascular-targeted delivery, where neutrophils are likely the first type of phagocyte encountered.