Localized delivery of therapeutics offers the possibility of increased drug effectiveness while minimizing side effects often associated with systemic drug administration. Factors that influence the likelihood of targeted therapeutics to reach the vascular wall include the ability to identify a: 1) disease-specific target epitope expressed by the vascular cells; 2) optimum drug carrier type, shape, and size for efficient interaction with the vascular wall; and 3) drug-carrier combination that allows for the effective release of therapeutics at the intended site. Existing literature has focused on identifying target epitopes and the degradation/drug release characteristics of a wide range of drug-carrier formulations. Our work focuses on probing the role of particle geometry, material chemistry and blood rheology/dynamics on the ability of vascular-targeted drug carriers to interact with the blood vessel wall – an important consideration that will control the effectiveness of drug targeting regardless of the targeted disease or delivered therapeutic. This presentation will highlight the carrier-blood cell interactions that affect drug carrier binding to the vascular wall and alter critical neutrophil functions in disease. The talk will present optimum drug carrier geometry for active and passive use of VTC in the treatment of many human diseases, including atherosclerosis and acute lung injury.