Vascular-targeted particle therapeutics offer the possibility of increased drug effectiveness while minimizing side effects often associated with systemic drug administration. Factors that influence the likelihood of targeted particle therapeutics to reach the vascular wall are the ability to identify: 1) a disease-specific target, 2) the appropriate drug carrier type and geometry for efficient interaction with the vascular wall, and 3) a drug-carrier combination that allows for the desired release of the targeted therapeutics. 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 therapeutically. 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 the material design parameters for optimal drug carriers' design for active and passive use in treating acute lung injury and other inflammatory diseases.