纳米医学在脑靶向药物递送中的意义:跨越血脑屏障

Dhirender Singh, B. Kevadiya, K. Nagpal, Navneet K. Sharma, ipkumar Patel
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引用次数: 5

摘要

过去二十年来,在药物开发领域取得了巨大而令人着迷的进步。尽管科学技术不断进步,但中枢神经系统疾病对临床医生提出了巨大的挑战。提高生活质量,停止或改善与年龄相关的神经退行性疾病,如痴呆症、阿尔茨海默氏症、帕金森病等,前景仍有待衡量。目前,全世界约有15亿人患有这样或那样的中枢神经系统疾病[1]。根据2017年的审查,全球约有4750万人患有痴呆症。预计2030年痴呆症患病率为7563万,到2050年将达到13546万,高于2009年世界阿尔茨海默病报告[2]的原始估计数字。具体来说,在美国,大约有520万人患有阿尔茨海默病(AD),它被认为是第六大死因,在65岁及以上的人群中排名第五。除非医学上取得突破,有利于实验疗法的药代动力学和药效学,否则据估计,到2050年,阿尔茨海默病患者的数量可能会从500万增加到预计的1400万[3,4]。在所有中枢神经系统相关疾病中,脑肿瘤是最具挑战性和致命性的疾病之一。2017年1月更新,美国有近70万人患有中枢神经系统相关肿瘤。据估计,到2017年底,将有近8万例原发性脑肿瘤被确诊。在32%的确诊病例中,预计三分之一是恶性的,近53000例是非恶性的。可悲的是,到2017年底,将近17000名中枢神经系统脑肿瘤患者将失去与生命的战斗[5]。无论科学研究和技术如何,大多数脑肿瘤都没有有效的临床治疗方法。绝大多数新的和现有的经验性治疗方法无法以合理的有效剂量到达/靶向大脑,这仍然是一个主要挑战。尽管从细胞水平到行为水平对脑生物学的理解取得了长足的进步,但基础科学的进展尚未以跨学科的方式得到充分发展,从实验室到临床的明确转化仍不确定[6]。当前交流的范围集中在脑药物传递的当前挑战,纳米药物在跨越血脑屏障的意义,他们的缺点和未来的前景也进行了讨论。
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The Significance of Nanomedicine in Brain-Targeted Drug Delivery: Crossing Blood-Brain Barriers
Last two decades have seen a tremendous and fascinating advancement in the field of drug development. Despite the progression in the scientific technology, the diseases of central nervous system (CNS) present a formidable challenge to the clinicians. Prospects to improve quality of life and halt or ameliorate age-related neurodegenerative diseases like Dementia, Alzheimer’s, Parkinson’s etc. are still far to measure. At present, around 1.5 billion people worldwide are suffering from one or another CNS disease [1]. As reviewed in 2017, around 47.5 million people around the globe are living with dementia. The prevalence of dementia is anticipated to be 75.63 million in 2030, reaching to 135.46 million by 2050, which is higher than original number estimated in the 2009 World Alzheimer report [2]. Specifically, in US about 5.2 million people are suffering from Alzheimer’s disease (AD), which has been cited as the sixth leading cause of death, and ranked fifth among those aged 65 years and older. Unless medical breakthroughs are made to favor the pharmacokinetics and pharmacodynamics of experimental therapeutics, it is estimated that by 2050, the number of AD patients may nearly triple from 5 million to a projected 14 million [3,4]. Of the all CNS related diseases, brain tumor is among the most challenging and lethal. Updated in January 2017, nearly 700,000 people in U.S. are living with CNS related tumor. It is estimated that nearly 80,000 cases of primary brain tumor would be diagnosed by the end of 2017. One third of the 32% of the diagnosed cases are anticipated to be malignant, and nearly 53,000 will be non-malignant. Sadly, by the end of 2017, nearly 17,000 people with CNS brain tumor will lose their battle with life [5]. Regardless of the scientific researches and technologies, no effective therapies are out in clinic for most of the brain tumors. The failure of vast majority of novel and current experiential therapeutics to reach/target the brain at a reasonable effective dose remains a major challenge. Despite great stride in understanding of the brain biology, from cellular to behavioral levels, the advances in basic science have not yet been fully developed in an interdisciplinary way, and a definitive translation from bench to bedside is still uncertain [6]. The scope of current communication focuses current challenges in brain-drug delivery, and significance of nanomedicine in crossing BBB, their downside and future prospects are also discussed.
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