The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.

中文翻译：

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脑药物输送的当前策略

血脑屏障（BBB）一直是脑部药物输送的一大障碍。健康大脑中的血脑屏障是一种扩散屏障，它通过阻止大多数化合物从血液转移到大脑来保护正常的大脑功能，这是必不可少的。只有小分子可以穿过血脑屏障。在某些中风，糖尿病，癫痫发作，多发性硬化，帕金森氏病和阿尔茨海默氏病等病理条件下，血脑屏障被破坏。这篇综述的目的是对过去五年来当前的脑部药物输送策略和相关主题进行广泛的概述。希望这篇评论可以激发读者发现将药物输送到大脑的可能方法。在对健康和病理状况下的血脑屏障结构和功能进行初步概述之后，本次审查将再次进行，根据最近的出版物，一些有争议的问题，例如纳米粒子本身是否可以穿越血脑屏障，以及是否通过主动靶向纳米粒子将药物特异性地转移到大脑。还审查了当前的非纳米粒子策略，例如在病理条件下通过可渗透BBB输送药物，以及使用非侵入性技术来增强脑部药物的吸收。最后，大脑药物输送中经常被忽视的一个特定领域是衰老对血脑屏障的影响，本综述基于文献中的有限研究，涵盖了衰老对血脑屏障的影响。还审查了当前的非纳米粒子策略，例如在病理条件下通过可渗透BBB输送药物，以及使用非侵入性技术来增强脑部药物的吸收。最后，大脑药物输送中经常被忽视的一个特定领域是衰老对血脑屏障的影响，本综述基于文献中的有限研究，涵盖了衰老对血脑屏障的影响。还审查了当前的非纳米粒子策略，例如在病理条件下通过可渗透BBB输送药物，以及使用非侵入性技术来增强脑部药物的吸收。最后，大脑药物输送中经常被忽视的一个特定领域是衰老对血脑屏障的影响，本综述基于文献中的有限研究，涵盖了衰老对血脑屏障的影响。