Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, Taiwan ; Department of Mechanical Engineering, Taiwan.
Graduate Institute of Medical Mechatronics, Chang Gung University, Taiwan.
Int J Nanomedicine. 2014;9:311-26. doi: 10.2147/IJN.S51258. Epub 2014 Jan 6.
Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a highperformance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses.
不完全的血管内皮细胞覆盖、血细胞黏附于血管支架以及动脉炎症可导致急性支架血栓形成。全身性给予乙酰水杨酸可减轻血管内皮功能障碍,潜在地减少血栓形成,增强血管舒张,并抑制动脉粥样硬化进展;但会因上消化道出血而减弱。本研究提出了一种具有生物可降解纳米纤维的杂交支架,用于局部、持续输送乙酰水杨酸至受损的动脉壁。生物可降解纳米纤维是通过先将聚(D,L)-丙交酯-共-乙交酯和乙酰水杨酸溶解在 1,1,1,3,3,3-六氟-2-丙醇中制备的。然后将该溶液电纺成纳米纤维管,然后将其安装到市售的裸金属支架上。通过洗脱法和高效液相色谱法对纳米纤维中药物的体外释放率进行了表征。实验结果表明,生物可降解纳米纤维可在三周内释放出高浓度的乙酰水杨酸。局部输送乙酰水杨酸可减少血小板和单核细胞黏附的体内功效,以及杂交支架在治疗裸露兔动脉时引起的最小组织炎症反应,均已得到证实。提出的具有生物可降解载有乙酰水杨酸的纳米纤维的杂交支架,可促进药物局部、持续输送,促进再内皮化,降低受损动脉的血栓形成性。这些支架可能在局部输送心血管药物方面具有应用潜力。此外,使用具有高载药量的载有乙酰水杨酸的纳米纤维的杂交支架可能为治疗急性支架血栓形成高危患者提供新的思路。