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

该奖项的目的是评估可生物降解的非球形药物载体的流体动力学行为和结合效率，这些药物载体旨在靶向中到大血管的血管壁。据推测，由于它们独特的流体动力学相互作用，椭圆形颗粒将具有上级的能力来结合通常与心血管疾病相关的中至大血管的壁，而不是通常提出的球形颗粒，同时保持穿过人毛细血管的能力。 具体的工作目标是：（1）以聚乙烯为原料制备可生物降解的椭球体（2）研究这些生物可降解的椭球体在生理流动中的旋转状态以及它们使用体外流动测定在不阻碍流动的情况下导航复杂微血管几何形状的能力;和（3）评价它们在体外和在人血细胞存在下靶向发炎的内皮（血管壁的细胞衬里）的有效性。 如果成功的话，这项工作将对可注射血管靶向药物载体的设计产生重大影响，这些药物载体用于许多人类疾病的高度局部化和有效的治疗。将治疗剂靶向体内特定部位的能力可以允许将高效治疗剂施用至患病细胞/组织而不影响健康细胞/组织;从而增强药物功效而没有有害的副作用。实现这一壮举可以显著降低由CAD等疾病引起的高死亡率，降低医疗成本，提高慢性炎症性疾病患者的生活质量。

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.