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

开发用于血管内抗再狭窄药物输送的微孔纳米复合材料球囊

• 批准号: 9474293
• 负责人: Mark Bates
• 金额: $ 60.22万
• 依托单位: PULSUS MEDICAL, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9474293
• 关键词: Adverse reactions; Angioplasty; Animals; Arteries; Back; Biological; Blood; Blood Vessels; Carbon Nanotubes; Caring; Catheters; Chemical Agents; Chemistry; Coagulation Process; Development; Devices; Dialysis procedure; Diffusion; Dimensions; Disease; Drug Delivery Systems; Dysbarism; Embolism; Evaluation; Excipients; Excision; Exhibits; FDA approved; Family suidae; Fee-for-Service Plans; Forearm; Health; Hemodialysis; In Situ; Intervention; Kidney Failure; Laboratories; Lesion; Liquid substance; Manufacturer Name; Measures; Mechanics; Medical; Medical Device; Methods; Modeling; Modification; Monitor; Nylons; Organ Transplantation; Output; Paclitaxel; Patients; Pharmaceutical Preparations; Phase; Physiologic pulse; Polymers; Procedures; Process; Prosthesis; Research Institute; Risk; Safety; Shunt Device; Site; Stenosis; Stents; Structure; Surface; Technology; Testing; Therapeutic Effect; Toxic effect; Tube; Twin Multiple Birth; Validation; Veins; aqueous; base; biocompatible polymer; biomaterial compatibility; common treatment; cost; design; hydrophilicity; improved; in vivo; individualized medicine; lipophilicity; mortality; nanocomposite; novel therapeutics; patient population; polymerization; pressure; restenosis; scale up; systemic toxicity

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-

血液透析是肾衰竭最常见的治疗方法，需要血液从体内传递出来， 通过过滤器，然后回到体内。几乎30％的血液透析患者患动脉移植 程序涉及插入动脉和静脉之间的假体分流（即合成管）的程序， 特别是在前臂。到2020年，血液透析患者人群估计将超过500,000 需要移植物的患者人数将超过150,000（500,000的30％），其中大多数将会达到 凝结发生在这些移植物中，这是由于出口处的血管中发生的堵塞 移植物的位置。结果，许多血液透析患者需要干预才能打开狭窄，或 血管的狭窄。 当前，封闭移植的干预措施涉及用设备去除克隆，然后进行血管成形术 静脉。一旦需要血管成形术，病变就会保持恢复态度，并且患者通常需要额外的declot 过程并重复血管成形术。虽然通常使用支架来打开狭窄的动脉，但它们不能 在这种情况下可以实施。需要更机械兼容的结构。相对较新，涂有毒品 气球（DCB）是可能的解决方案。但是，DCB固有地暴露了零星和不可预测的药物 送货。此外，DCB药物的输送目前效率很低，大部分药物丢失了 下游。这增加了全身毒性的潜力。此外，化学剂（赋形剂）是 需要控制药物涂层的扩散。这些赋形剂构成下游栓塞的风险 病人。需要一种更高效，安全的血管内抗归还药物的方法来改善 功效并降低栓塞风险。 我们建议开发带有微孔的基于纳米复合材料的聚合物气囊，以实现脉冲流动 使用我们的方法，可以将药物直接直接运送到患病部位 降低了全身毒性的潜力。我们的血管内药物输送系统能够交付 几乎任何形式的药物，从亲脂性药物到亲水性药物，甚至组合。 -1-