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，这些载体设计用于靶向中大型血管的血管壁。据推测，由于其独特的流体动力学相互作用，椭圆形颗粒将具有优越的能力，结合中到大血管的血管，通常与心血管疾病相关的典型建议的球形颗粒，同时保持穿越人体毛细血管的能力。拟议工作的具体目标是：(1)利用简单的水包油溶剂挥发法制备聚(丙交酯-乙醇酸)聚合物制备可生物降解椭球；(2)研究这些可生物降解椭球在生理流动中的旋转状态，以及使用体外流动分析技术研究它们在不阻碍流动的情况下导航复杂微血管几何形状的能力；以及(3)评估它们在体外和在人体血细胞存在下靶向炎症的内皮(血管壁细胞衬里)的有效性。如果成功，这项拟议的工作将对可注射血管靶向药物载体的设计产生重大影响，这些药物载体用于高度本地化和高效地输送治疗药物，治疗许多人类疾病。将治疗药物定向到体内特定部位的能力，可以在不影响健康细胞/组织的情况下，对患病细胞/组织给予高度有效的治疗药物，从而提高药物疗效，而不会产生有害的副作用。实现这一壮举可以显著降低冠心病等疾病的高死亡率，降低医疗成本，并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.