Development of a microperforated nanocomposite balloon for intravascular anti-restenotic drug delivery

血液透析是肾衰竭最常见的治疗方法，需要将血液排出体外， 通过过滤器回到体内近30%的血液透析患者接受动静脉移植 涉及假体分流器插入的手术（即，合成管）， 特别是在前臂。到2020年，血液透析患者人数估计将超过50万， 需要移植的患者数量将超过150，000（500，000的30%），其中大多数移植将 最终凝结。由于流出道血管发生堵塞，这些移植物中会发生凝血 移植部位。因此，许多血液透析患者需要干预以打开狭窄，或 血管狭窄。 目前，对凝块移植物的干预包括用装置去除凝块，然后进行血管成形术。 静脉一旦需要进行血管成形术，病变将继续再狭窄，患者通常需要额外的解栓 重复血管成形术。虽然支架通常用于打开狭窄的动脉，但它们不能 在这种情况下实施。需要更机械顺应的结构。相对较新，药物涂层 气球（DCB）是一种可能的解决方案。然而，DCB固有地表现出偶发的和不可预测的药物毒性。 交付.此外，DCB药物递送目前相当低效，大部分药物丢失 下游这增加了全身毒性的可能性。此外，化学试剂（赋形剂） 需要控制药物涂层的扩散。这些赋形剂会造成下游栓塞的风险， 病人需要一种更有效、更安全的血管内抗再狭窄药物输送方法来改善 有效性和降低栓塞风险。 我们建议开发一种具有微穿孔的纳米复合材料聚合物球囊， 药物输送到病变。使用我们的方法，药物可以有效地直接输送到患病部位 减少全身毒性的可能性。我们的血管内药物输送系统能够输送 几乎任何形式的药物，从亲脂性药物到亲水性药物，甚至其组合。 -1-

Hemodialysis is the most common treatment for kidney failure, requiring the passing of blood out of the body, through a filter, and back into the body. Almost 30% of hemodialysis patients undergo arteriovenous graft procedures involving the insertion of prosthetic shunts (i.e., synthetic tubes) between artery and vein, particularly in the forearm. With the hemodialysis patient population estimated to reach over 500,000 by 2020, the number of patients requiring grafts will reach over 150,000 (30% of 500,000) and most of these grafts will eventually clot. Clotting occurs in these grafts due to blockages that occur in the blood vessel at the outflow site of the graft. As a result, many hemodialysis patients require intervention to open up the narrowing, or stenosis, of the blood vessel. Currently, interventions for clotted grafts involve removal of the clot with a device followed by angioplasty of the vein. Once angioplasty is needed, the lesion will keep restenosing and often the patients need additional declot procedures and repeat angioplasty. While stents are routinely used to open up narrowed arteries, they cannot be implemented in this case. A more mechanically compliant structure is needed. Relatively new, drug-coated balloons (DCBs) are a possible solution. However, DCBs inherently exhibit sporadic and unpredictable drug delivery. Furthermore, DCB drug delivery is currently quite inefficient with much of the drug being lost downstream. This increases the potential for systemic toxicity. In addition, chemical agents (excipients) are needed to control diffusion of the drug coating. These excipients pose a risk of downstream embolism for the patient. A more efficient, safer method of intravascular anti-restenotic drug delivery is needed to improve efficacy and reduce risk of embolism. We propose to develop a nanocomposite-based polymer balloon with microperforations to enable pulsed-flow drug delivery to the lesion. Using our approach, drugs can be efficiently delivered directly to the diseased site reducing the potential for systemic toxicity. Our intravascular drug delivery system is capable of delivering drugs of almost any form, from lipophilic drugs to hydrophilic drugs and even combinations thereof.  -1-