Tissue plasminogen activator-based clot busting: Controlled delivery approaches.
Tissue plasminogen activator-based clot busting: Controlled delivery approaches.
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DOI：
10.5339/gcsp.2014.46
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Yacoub MH
中科院分区：
文献类型：
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作者：
El-Sherbiny IM;Elkholi IE;Yacoub MH
心血管疾病是世界范围内主要的死亡原因。血栓形成是指血液在循环系统中形成凝块(血栓)，阻碍血流，是各种缺血性动脉综合征(如缺血性中风和心肌梗死)以及静脉综合征(如深静脉血栓形成)的主要原因之一，从而导致肺血栓。已开发出几种用于治疗血栓形成的溶栓剂，最常见的是组织纤溶酶原激活剂(TPA)，通过直接在血栓近端静脉输注系统或局部给药，目的是恢复和改善血流。TPA通过诱导纤溶酶原转化为蛋白酶纤溶酶，继而消化纤维蛋白，最终导致血栓溶解，从而触发血栓的溶解。尽管tPA具有很强的溶栓活性，但它也有很多缺点，包括药代动力学不佳，不利于冠状动脉正常血流的重建，不利于止血，导致危及生命的出血后果。出血的后果归因于tPA在全身循环的能力，因此可以溶解循环系统中的所有血栓，即使是防止出血和促进损伤修复的好血栓也是如此。本文综述了tPA的不同给药方法，包括：脂质体、超声触发溶栓、抗纤维蛋白抗体靶向tPA、伪装tPA、载药tPA微载体和纳米调控给药方法。
Cardiovascular diseases are the leading cause of death worldwide. Thrombosis, the formation of blood clot (thrombus) in the circulatory system obstructing the blood flow, is one of the main causes behind various ischemic arterial syndromes such as ischemic stroke and myocardial infarction, as well as vein syndromes such as deep vein thrombosis, and consequently, pulmonary emboli. Several thrombolytic agents have been developed for treating thrombosis, the most common being tissue plasminogen activator (tPA), administrated systemically or locally via IV infusion directly proximal to the thrombus, with the aim of restoring and improving the blood flow. TPA triggers the dissolution of thrombi by inducing the conversion of plasminogen to protease plasmin followed by fibrin digestion that eventually leads to clot lysis. Although tPA provides powerful thrombolytic activity, it has many shortcomings, including poor pharmacokinetic profiles, impairment of the reestablishment of normal coronary flow, and impairment of hemostasis, leading to life-threatening bleeding consequences. The bleeding consequence is ascribed to the ability of tPA to circulate throughout the body and therefore can lysis all blood clots in the circulation system, even the good ones that prevent the bleeding and promote injury repair. This review provides an overview of the different delivery approaches for tPA including: liposomes, ultrasound-triggered thrombolysis, anti-fibrin antibody-targeted tPA, camouflaged-tPA, tpA-loaded microcarriers, and nano-modulated delivery approaches.