(253c) Particle Size and the Efficacy of Vascular –Targeted Drug Carriers: Application in Cardiovascular Diseases
AIChE Annual Meeting
2009
2009 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Disease Therapies
Tuesday, November 10, 2009 - 1:10pm to 1:30pm
Overall, localized delivery of therapeutics offer the possibility of increased drug effectiveness while minimizing side effects often associated with systemic drug administration. Factors that affect the possibility of targeting 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 have focused mainly on identifying target epitopes and the degradation/drug release characteristics of a wide range of drug-carrier formulations. Absent in the literature, are work focused on the potential roles of particle size on the ability of vascular-targeted drug carriers to interact with the vessels ? an important consideration that will control the effectiveness of drug targeting regardless of the targeted disease or delivered therapeutic. Nanometer to submicron-sized spherical particles are widely proposed for use in vascular drug delivery, yet very little evidence has been presented in the literature as to their optimal use for vascular-targeted drug delivery. This work focuses on elucidating the effect of particle size along with blood flow dynamics, vessel size and hematocrit on the efficiency of drug carrier interaction with inflamed endothelium in vitro. We find that the binding efficiency of particles to inflamed endothelium from blood flow increase with increasing particle size at low and intermediate shear stresses for particle sizes from 100nm up to 10 micron. Furthermore, nano-sized particles show minimal binding in horizontal (anti-gravity) and vertical channels on the order of medium venules and arteries when compared to larger-sized spheres. Overall, the presented data suggest that spherical particles larger than 5 microns are optimal for vascular-targeted drug delivery applications in medium to large vessel relevant to cardiovascular diseases.