BRIGE: Engineering Spheroidal Particles for Drug Delivery - A Novel Approach to Vascular Targeted Therapies

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

The objective of this award is to evaluate the hydrodynamic behavior and binding efficiency of biodegradable, non-spherical drug carriers designed for targeting the vascular wall in medium to large vessels. It is hypothesized that due to their unique hydrodynamic interactions ellipsoidal particles will possess a superior ability to bind the wall in medium to large blood vessels often associated with cardiovascular diseases over typically proposed spherical particles while maintaining the ability to traverse human capillaries. The specific aims of the proposed work are: (1) to fabricate biodegradable ellipsoids from poly(lactide-co-glycolic acid) polymer using the simple oil-in-water solvent evaporation fabrication method; (2) to investigate the rotational state of these biodegradable ellipsoids in physiological flow and their ability to navigate complex microvessel geometry without obstructing flow using in vitro flow assays; and (3) to evaluate their effectiveness in targeting inflamed endothelium (cell lining of the blood vessel wall) in vitro and in the presence of human blood cells. If successful, the proposed work will significantly impact the design of injectible vascular-targeted drug carriers for highly localized and efficient delivery of therapeutics in many human diseases. The ability to target therapeutics to specific sites in the body can allow for the administration of highly potent therapeutic agents to diseased cells/tissues without affecting healthy ones; thereby, enhancing drug efficacy with no deleterious side effects. Achieving this feat can lead to a significant decrease in the high mortality rate attributed to diseases like CAD, lowered healthcare cost and improved quality of life for individuals affected with chronic inflammatory diseases.