Huang Ting, Li Ni, Gao Jianqing
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Department of Cardiothoracic Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo 315041, China.
Asian J Pharm Sci. 2019 May;14(3):233-247. doi: 10.1016/j.ajps.2018.12.004. Epub 2019 Feb 4.
Thrombus formed in blood vessel is a progressive process, which would lead to life-threatening thrombotic diseases such as ischemic stroke. Unlike other diseases, the recognition of thrombus is usually in the late stage where blood vessels are largely blocked. So acute thrombotic diseases have a narrow therapeutic window, and remain leading causes of morbidity and mortality, whereas current thrombolysis therapy has limited therapeutic effects and bleeding complications. Thrombolytic agents in unwanted sites would cause hemorrhage due to the activation of plasminogen. Moreover, untargeted thrombolysis therapy require large amounts of thrombolytic agents, which in return would enhance hemorrhage risk. To improve the efficiency while minimizing the adverse effects of traditional thrombolysis therapy, novel drug delivery systems have been investigated. Various targeting strategies including ultrasound and magnetic field directed targeting, and specific binding, have been designed to deliver thrombolytic drugs to the thrombotic sites. These strategies demonstrate promising results in reducing bleeding risk as well as allowing less dosage of thrombolytic drugs with lowered clot lysis time. In this review, we discuss recent progress on targeted delivery of thrombolytics, and summarize treatment advantages and shortcomings, potentially helping to further promote the development of targeted thrombolysis.
血管中形成的血栓是一个渐进的过程，它会导致危及生命的血栓性疾病，如缺血性中风。与其他疾病不同，血栓的识别通常在血管大部分被阻塞的晚期。因此，急性血栓性疾病的治疗窗口期很窄，仍然是发病和死亡的主要原因，而目前的溶栓治疗效果有限且存在出血并发症。溶栓药物在非靶部位会因纤溶酶原的激活而导致出血。此外，非靶向溶栓治疗需要大量的溶栓药物，这反过来又会增加出血风险。为了提高传统溶栓治疗的效率并将其副作用降至最低，人们对新型药物递送系统进行了研究。已经设计了各种靶向策略，包括超声和磁场导向靶向以及特异性结合，以将溶栓药物递送至血栓部位。这些策略在降低出血风险以及减少溶栓药物用量并缩短血栓溶解时间方面显示出了有前景的结果。在本综述中，我们讨论了溶栓药物靶向递送的最新进展，并总结了治疗的优缺点，可能有助于进一步推动靶向溶栓的发展。
