Chia-Hung Liu , Lekshmi Rethi , Pei-Wei Weng , Hieu Trung Nguyen , Andrew E.-Y. Chuang
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引用次数: 0
Abstract
Thrombotic blockages within blood vessels give rise to critical cardiovascular disorders, including ischemic stroke, venous thromboembolism, and myocardial infarction. The current approach to the therapy of thrombolysis involves administering Plasminogen Activators (PA), but it is hindered by fast drug elimination, narrow treatment window, and the potential for bleeding complications. Leveraging nanomedicine to encapsulate and deliver PA offers a solution by improving the efficacy of therapy, safeguarding the medicine from proteinase biodegradation, and reducing unwanted effects in in vivo trials. In this review, we delve into the underlying venous as well as arterial thrombus pathophysiology and provide an overview of clinically approved PA used to address acute thrombotic conditions. We explore the existing challenges and potential directions within recent pivotal research on a variety of targeted nanocarriers, such as lipid, polymeric, inorganic, and biological carriers, designed for precise delivery of PA to specific sites. We also discuss the promising role of microbubbles and ultrasound-assisted Sono thrombolysis, which have exhibited enhanced thrombolysis in clinical studies. Furthermore, our review delves into approaches for the strategic development of nano-based carriers tailored for targeting thrombolytic action and efficient encapsulation of PA, considering the intricate interaction in biology systems as well as nanomaterials. In conclusion, the field of nanomedicine offers a valuable method for the exact and effective therapy of severe thrombus conditions, presenting a pathway toward improved patient outcomes and reduced complications.
血管内的血栓堵塞会引发严重的心血管疾病，包括缺血性中风、静脉血栓栓塞症和心肌梗塞。目前的溶栓治疗方法包括使用血浆酶原激活剂（PA），但这种方法存在药物消除快、治疗窗口狭窄以及可能出现出血并发症等问题。利用纳米药物封装和递送 PA 可提高疗效，防止药物被蛋白酶生物降解，并减少体内试验中的不良反应，从而提供一种解决方案。在本综述中，我们深入探讨了静脉和动脉血栓的基本病理生理学，并概述了临床批准用于治疗急性血栓病症的 PA。我们探讨了近期对各种靶向纳米载体（如脂质、聚合物、无机和生物载体）进行关键性研究的现有挑战和潜在方向，这些载体旨在将 PA 精准地输送到特定部位。我们还讨论了微气泡和超声辅助索诺溶栓疗法的前景，这些疗法在临床研究中显示出更强的溶栓能力。此外，考虑到生物系统和纳米材料之间错综复杂的相互作用，我们的综述还深入探讨了纳米载体的战略开发方法，这些载体专为靶向溶栓作用和有效封装 PA 而量身定制。总之，纳米医学领域为准确有效地治疗严重血栓提供了一种宝贵的方法，为改善患者预后和减少并发症提供了一条途径。
期刊介绍：
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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