Farb A, Heller P F, Shroff S, Cheng L, Kolodgie F D, Carter A J, Scott D S, Froehlich J, Virmani R
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
Circulation. 2001 Jul 24;104(4):473-9. doi: 10.1161/hc3001.092037.
Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored.
Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 microgram of paclitaxel
CSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.
紫杉醇在体外可抑制血管平滑肌增殖，早期研究表明紫杉醇可能有助于预防再狭窄。通过支架递送紫杉醇相关的早期和晚期内膜生长及局部血管病理变化尚未得到充分研究。
采用球囊扩张式不锈钢支架进行局部药物递送，该支架涂覆有交联的可生物降解聚合物、硫酸软骨素和明胶（CSG），含有不同剂量的紫杉醇。将涂有含紫杉醇（每个支架含42.0、20.2、8.6或1.5微克紫杉醇）的CSG支架、不含紫杉醇的CSG涂层支架以及未涂层支架（不含紫杉醇或CSG）植入新西兰白兔的髂动脉，植入后28天处死动物。与不含紫杉醇的CSG涂层支架相比，每个支架含42.0和20.2微克紫杉醇的支架在支架支柱部位的平均新生内膜厚度分别减少了49%（P<0.0003）和36%（P<0.007）。然而，组织学结果表明，高剂量（42.0和20.2微克）含紫杉醇支架存在不完全愈合，表现为内膜持续纤维蛋白沉积、内膜内出血以及内膜和外膜炎症增加。单独涂有CSG（不含紫杉醇）的支架与未涂层支架的新生内膜生长相似。在另一组90天时处死的兔子中，含42.0或21.0微克紫杉醇的CSG涂层支架不再抑制新生内膜生长。
CSG涂层似乎是一种有前景的局部药物递送介质。紫杉醇聚合物涂层支架可减少新生内膜形成，但在28天时存在不完全愈合的证据。然而，在90天时新生内膜抑制作用未持续存在。
