Ye Wei, Wang Nan, Hu Kebang, Zhang Lincai, Liu Aihui, Pan Changjiang, Gong Tao, Liu Tao, Ding Hongyan
Jiangsu Provincial Key Lab for Interventional Medical Devices, Huaiyin Institute of Technology Huaian 223003 China
Department of Urology, The First Hospital of Jilin University Changchun 130021 PR China
RSC Adv. 2018 Jul 31;8(48):27253-27259. doi: 10.1039/c8ra04273j. eCollection 2018 Jul 30.
Thrombosis or embolism is the leading cause of death and long-term adult disability worldwide. To reduce the risk of thrombosis and hemorrhaging in patients, a facile and versatile method was developed to fabricate microcapsules for targeted antithrombotic drug delivery. The microcapsules were prepared oxidative polymerization of dopamine on polystyrene microspheres, followed by immobilization of fibrinogen onto the surface of poly(dopamine) layers. Subsequently, microcapsules were obtained by removing the cores with THF. Nattokinase was loaded into the microcapsules diffusion. The loading amount was approximately 0.05 mg g at 37 °C, and the loading efficiency was nearly 75%, based on the initial concentration of nattokinase in PBS. The release of nattokinase was a gradual process at 37 °C, and the activity of the targeted activated platelets was highly efficient. The antithrombotic activity of the nattokinase microcapsules was evidenced by the sharp dissolution of fibrin clots and the blood clotting time indexes. A gradual release mechanism of platelet-inspired microcapsules used for targeted antithrombotic therapy was proposed. This strategy for targeted antithrombotic drug delivery, which lowers the demand dose and minimizes side effects while maximizing drug efficacy, provides a potential new way to treat life-threatening diseases caused by vascular disruption.
血栓形成或栓塞是全球范围内成年人死亡和长期残疾的主要原因。为降低患者发生血栓形成和出血的风险，人们开发了一种简便且通用的方法来制备用于靶向抗血栓药物递送的微胶囊。通过在聚苯乙烯微球上进行多巴胺的氧化聚合制备微胶囊，随后将纤维蛋白原固定在聚多巴胺层表面。接着，用四氢呋喃去除芯材从而获得微胶囊。通过扩散将纳豆激酶载入微胶囊。基于 PBS 中纳豆激酶的初始浓度，在 37°C 时载药量约为 0.05 mg/g，载药效率接近 75%。纳豆激酶在 37°C 时的释放是一个渐进过程，并且对靶向活化血小板的活性高效。纤维蛋白凝块的迅速溶解和凝血时间指标证明了纳豆激酶微胶囊的抗血栓活性。提出了用于靶向抗血栓治疗的血小板启发式微胶囊的渐进释放机制。这种靶向抗血栓药物递送策略在降低所需剂量、使副作用最小化同时使药物疗效最大化，为治疗由血管破裂引起的危及生命的疾病提供了一种潜在的新方法。
