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Targeting Therapeutics Across the Blood Brain Barrier (BBB) Prerequisite Towards Thrombolytic Therapy for Cerebrovascular Disorders—an Overview and Advancements

机译:跨血脑屏障(BBB)的靶向治疗脑血管疾病溶栓治疗的先决条件—概述和进展

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摘要

Cerebral tissues possess highly selective and dynamic protection known as blood brain barrier (BBB) that regulates brain homeostasis and provides protection against invading pathogens and various chemicals including drug molecules. Such natural protection strictly monitors entry of drug molecules often required for the management of several diseases and disorders including cerebral vascular and neurological disorders. However, in recent times, the ischemic cerebrovascular disease and clinical manifestation of acute arterial thrombosis are the most common causes of mortality and morbidity worldwide. The management of cerebral Ischemia requires immediate infusion of external thrombolytic into systemic circulation and must cross the blood brain barrier. The major challenge with available thrombolytic is their poor affinity towards the blood brain barrier and cerebral tissue subsequently. In the clinical practice, a high dose of thrombolytic often prescribed to deliver drugs across the blood brain barrier which results in drug dependent toxicity leading to damage of neuronal tissues. In recent times, more emphasis was given to utilize blood brain barrier transport mechanism to deliver drugs in neuronal tissue. The blood brain barrier expresses a series of receptor on membrane became an ideal target for selective drug delivery. In this review, the author has given more emphasis molecular biology of receptor on blood brain barrier and their potential as a carrier for drug molecules to cerebral tissues. Further, the use of nanoscale design and real-time monitoring for developed therapeutic to encounter drug dependent toxicity has been reviewed in this study.
机译:脑组织具有称为血脑屏障(BBB)的高度选择性和动态保护功能,该功能可调节脑稳态,并提供针对入侵病原体和各种化学物质(包括药物分子)的保护作用。这种自然保护措施严格监控通常需要管理几种疾病和病症(包括脑血管和神经疾病)的药物分子的进入。然而,最近,缺血性脑血管疾病和急性动脉血栓形成的临床表现是全世界范围内死亡和发病的最常见原因。脑缺血的治疗需要将外部溶栓剂立即注入全身循环系统,并且必须穿过血脑屏障。可用的溶栓剂的主要挑战是它们对血脑屏障和随后的脑组织的亲和力差。在临床实践中,经常开出高剂量的溶栓剂以通过血脑屏障递送药物,这会导致药物依赖性毒性,从而导致神经元组织受损。近来,人们更加重视利用血脑屏障转运机制在神经元组织中输送药物。血脑屏障在膜上表达一系列受体,成为选择性药物递送的理想靶标。在这篇综述中,作者更加强调了血脑屏障受体的分子生物学及其作为药物分子向脑组织的载体的潜力。此外,在这项研究中已经综述了使用纳米级设计和实时监测开发的治疗剂遇到药物依赖性毒性的方法。

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