Model Particulate Drug Carriers Modulate Leukocyte Adhesion in Human Blood Flows

Drug carriers have been widely explored as a method of improving the efficacy of therapeutic drugs for a variety of diseases, including those involving inflammation. However, few of these formulations have advanced past clinical trials. There are still major gaps in our understanding of how drug carriers impact leukocytes, particularly in inflammatory conditions. In this work, we investigated how targeted and nontargeted drug carriers affect the function of leukocytes in blood flow. We explored three primary mechanisms: (1) collisions in blood flow disrupt leukocyte adhesion, (2) specific binding to the endothelium competes with leukocytes for binding sites, and (3) particle phagocytosis alters leukocyte phenotype, resulting in reduced adhesion. We find that each of these mechanisms contributes to significantly reduced leukocyte adhesion to an inflamed endothelium, and that particle phagocytosis may be the most significant driver of this effect. These results are crucial for understanding the totality of the impact of drug carriers on leukocyte behavior and response to inflammation and should inform the future design of any such drug carriers.