Probing Cellular-Particle Interactions and Deformability in the Design of Vascular-Targeted Carriers

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 possibility of targeted therapeutics to reach the vascular wall include the ability to 1) identify disease-specific target epitope expressed by the vascular cells; 2) identify optimum drug carrier type, shape and size for efficient interaction with the vascular wall; and 3) identify a drug-carrier combination that allow 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 deformability, 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 key carrier-blood cell and carrier-plasma protein interactions that affect drug carrier binding to the vascular wall and suggest the optimum drug carrier modulus and material chemistry for vascular-targeted drug delivery applications in a solid tumor microvascular network and in large vessels associated with many cardiovascular diseases.