- 期刊
具抗凝血與抗血管內膜增生之雙效型藥物釋放血管支架
A Dual Drug-eluting Stent with Anti-thrombotic and Anti-proliferative Effects
摘要
臨床研究指出，目前藥物釋放型血管支架所使用的高分子塗層，易刺激血管壁，引發程度不一之過敏或是發炎反應，導致晚期的血栓或血管再狹窄。為了降低高分子所造成之不良反應，本研究乃以特殊的疏水性肝素（Duraflo^TM heparin）取代傳統的高分子塗層，包覆抑制血管內膜過度增生藥（sirolimus），僅於Duraflo^TM heparin塗層外添加一層超薄的聚乳酸（polylactic acid，PLA）作為阻絕層，以隔絕血液中的離子親和分子對heparin的影響，製備出一具有超薄高分子塗層之雙效型藥物釋放血管支架。本研究利用少量多層的噴塗方式，分別將Duraflo^TM heparin與sirolimus塗佈於支架表面，實驗證實塗層與支架表面具有足夠的附著力，可承受氣球導管擴張之撐開測試，並無剝落或分離的情形。隨著噴塗層數的提高，藥物的塗佈量會呈線性上升，藉此方式可成功製備出三種不同劑量的藥物釋放型血管支架。由體外藥物釋放實驗證實，Duraflo^TM heparin能持續且緩慢地由支架表面釋放。由高分子塗層之阻隔效果測試證實，超薄的聚乳酸確實具有阻絕血清的功效，能有效防止血清中的蛋白質競爭heparin，降低Duraflo^TM heparin在血清中的流失量，應可延長藥物在體內之釋放時間。以上結果證實，本研究所開發出的藥物釋放血管支架，可同時釋放抗凝血與抑制內膜增生雙重藥物，不須藉由高分子做為包藥載體，能降低對血管壁的刺激，很有潛力成為新一代的藥物釋放型血管支架。
並列摘要
To reduce the deleterious effects induced by the polymeric coating, a dual drug-eluting stent (DES) which utilizes unique Duraflo^TM heparin coating layers as a drug reservoir was developed in this study. Using a spray-coating method, Duraflo^TM heparin and sirolimus solution were coated layer-by-layer alternatively onto the surface of a metallic stent. An ultra-thin polymeric topcoat was then used as a barrier to prevent the leaching of heparin when in contact with the blood. Scanning electron microscopic examination showed that the spray-coated Duraflo^TM heparin was tightly adhered to the stent surface and allowed balloon expansion of the stent without cracking or peeling from the wire. It was found that the amount of the drugs loaded on the stent was linearly related to the amount of sprayed drugs or the number of layers of coated drugs. Additionally, the ultra-thin PLA topcoat can serve as barrier to prevent rapid release and serum leaching of Duraflo^TM heparin from stent surface. The aforementioned results indicated that the developed DES can simultaneously provide the anti-thrombotic and anti-proliferative effects without recourse to polymeric carrier, suggesting that such dual DESs can be a potential alternative for the treatment of coronary artery disease.