Speck Ulrich, Häckel Akvile, Schellenberger Eyk, Kamann Stefanie, Löchel Melanie, Clever Yvonne P, Peters Daniel, Scheller Bruno, Trog Sabrina, Bettink Stephanie
Department of Radiology, Experimental Radiology, Charité, 10098, Berlin, Germany.
Innora GmbH, Berlin, Germany.
Cardiovasc Intervent Radiol. 2018 Oct;41(10):1599-1610. doi: 10.1007/s00270-018-2018-9. Epub 2018 Jul 2.
To experimentally investigate a new homogenously paclitaxel/resveratrol-coated balloon catheter in terms of transport of the coating to the treated tissue and local effects including histology and functional tests.
Adherence of the coating to the balloon was explored by in vitro simulation of its passage to the lesion. Paclitaxel and resveratrol transfer to the vessel wall was investigated in porcine coronary and peripheral arteries. Matrix-assisted laser desorption/ionization (MALDI) was used for direct microscopic visualization of paclitaxel in arterial tissue. Inhibition of neointimal proliferation and tolerance of complete coating and resveratrol-only coating was investigated in pigs 4 weeks after treatment, and the effect of resveratrol on inflammation and healing after 3 and 7 days.
Drug loss on the way to the lesion was < 10% of dose, while 65 ± 13% was detected at the site of balloon inflation. After treatment similar proportions of drug were detected in coronary and peripheral arteries, i.e., 7.4 ± 4.6% of dose or 125 ± 74 ng/mg tissue. MALDI showed circumferential deposition. Inhibition of neointimal proliferation by paclitaxel/resveratrol coating was significant (p = 0.001) whereas resveratrol-only coating did not inhibit neointimal proliferation. During the first week after treatment of peripheral arteries with resveratrol-only balloons, we observed nominally less inflammation and fibrin deposition along with a significant macrophage reduction and more pronounced re-endothelialization. No safety issues emerged including left ventricular ejection fraction for detection of potential distal embolization after high-dose treatment of coronary arteries.
Paclitaxel/resveratrol-coated balloons were effective and safe in animal studies. Beyond acting as excipient resveratrol may contribute to vascular healing.
通过实验研究一种新型的均匀涂覆紫杉醇/白藜芦醇的球囊导管，考察涂层向治疗组织的输送情况以及包括组织学和功能测试在内的局部效应。
通过体外模拟其进入病变部位的过程，探究涂层与球囊的粘附情况。在猪的冠状动脉和外周动脉中研究紫杉醇和白藜芦醇向血管壁的转移。采用基质辅助激光解吸/电离（MALDI）技术直接在显微镜下观察动脉组织中的紫杉醇。在治疗4周后，研究紫杉醇/白藜芦醇涂层对猪新生内膜增殖的抑制作用以及完全涂层和仅含白藜芦醇涂层的耐受性，并研究白藜芦醇在治疗3天和7天后对炎症和愈合的影响。
在到达病变部位的过程中，药物损失<剂量的10%，而在球囊膨胀部位检测到65±13%的药物。治疗后，在冠状动脉和外周动脉中检测到的药物比例相似，即剂量的7.4±4.6%或125±74 ng/mg组织。MALDI显示为周向沉积。紫杉醇/白藜芦醇涂层对新生内膜增殖的抑制作用显著（p = 0.001），而仅含白藜芦醇涂层未抑制新生内膜增殖。在用仅含白藜芦醇的球囊治疗外周动脉后的第一周，我们观察到炎症和纤维蛋白沉积明显减少，巨噬细胞显著减少，再内皮化更明显。未出现安全问题，包括在高剂量治疗冠状动脉后检测潜在远端栓塞的左心室射血分数。
在动物研究中，紫杉醇/白藜芦醇涂层球囊有效且安全。除了作为辅料外，白藜芦醇可能有助于血管愈合。
