Drug Eluting Embolization Coils for Improved Treatment of Intracranial Aneurysms

项目摘要 脑动脉瘤是一种高风险疾病，其中脑中的血管膨胀有破裂的风险。的 如果不进行治疗，破裂后的死亡率为40-60%。目前治疗破裂和 未破裂的动脉瘤包括手术夹闭（血管外治疗）和基于导管的干预 （血管内治疗）。在血管内治疗，这是这项工作的重点，铂线圈插入 进入动脉瘤以诱导凝血并将动脉瘤从循环中排除。的首要挑战 与血管内动脉瘤治疗相关的是动脉瘤复发的风险， 动脉瘤囊中凝块的压实和酶消化。颅内动脉瘤复发 会增加出血性中风的风险该提案将评估药物洗脱弹簧圈的安全性和有效性 改善颅内动脉瘤介入治疗的结局。我们认为，持续释放 从药物洗脱的血管内线圈递送的天然存在的交联剂将增加血管内的 血栓的机械坚固性，减少纤维蛋白溶解，并最终降低复发的风险。凝块， 增加的化学-机械稳定性将抵抗与线圈压实和酶相关的失效模式 降解将在动物模型中评价京尼平洗脱弹簧圈的安全性和有效性， 临床相关的，并模仿人体缺陷的解剖结构。京尼平洗脱弹簧圈的安全性和有效性 将作为剂量和递送动力学的函数进行评价。体外疗效将使用 在灌注下操作的模型动脉瘤囊中的模拟盘绕动脉瘤。体内实验将在 使用兔弹性蛋白酶动脉瘤模型进行。疗效将通过血管造影、组织学和 动脉瘤中血栓的化学机械测量。该项目将最终衡量 药物洗脱弹簧圈作为治疗未破裂血管的潜在上级技术的体内安全性和有效性 无脉畸形后续人体临床研究将进一步确定京尼平洗脱的安全性和有效性 栓塞弹簧圈。药物洗脱弹簧圈有可能改变未破裂颅内出血的治疗 动脉瘤，并大大降低出血性中风的风险。

PROJECT SUMMARY Brain aneurysms are a high-risk condition in which bulging blood vessels in the brain are at risk of rupture. The mortality rate after rupture is 40-60% if no treatment is administered. Current treatment for both ruptured and unruptured aneurysms includes surgical clipping (exovascular therapy) and catheter-based intervention (endovascular therapy). In endovascular therapy, which is the focus of this work, platinum coils are inserted into the aneurysm to induce clotting and exclude the aneurysm from circulation. The primary challenge associated with endovascular aneurysm therapy is the risk of aneurysm recurrence due to mechanical compaction and enzymatic digestion of the clot in the aneurysm sac. Recurrence in intracranial aneurysms elevates the risk of hemorrhagic stroke. This proposal will evaluate the safety and efficacy of a drug-eluting coil to improve outcomes when treating intracranial aneurysms prophylactically. We posit that sustained release of naturally occurring crosslinking agents delivered from drug-eluting endovascular coils will increase the mechanical robustness of the clots, reduce fibrinolysis, and ultimately reduce the risk of recurrence. Clots with increased chemo-mechanical stability will resist failure modes associated with coil compaction and enzymatic degradation. The safety and efficacy of genipin-eluting coils will be evaluated in animal models that are clinically relevant and mimic the anatomy of defects in humans. The safety and efficacy of genipin-eluting coils will be evaluated as a function of dosing and delivery kinetics. In vitro efficacy will be measured using a simulated coiled aneurysm in a model aneurysm sac operating under perfusion. In vivo experiments will be performed using a rabbit elastase aneurysm model. Efficacy will be quantified by angiography, histology, and chemo-mechanical measurements of thrombus in the aneurysms. This project will ultimately measure the in vivo safety and efficacy of drug-eluting coils as a potentially superior technology to treat unruptured anuerysms. Follow-on clinical studies in humans will further establish the safety and efficacy of genipin-eluting embolization coils. Drug-eluting coils have the potential to transform the treatment of unruptured intracranial aneurysms and dramatically reduce the risk of hemorrhagic stroke.