Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA.
Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA; College of Pharmacy and Chemistry, Dali University, Dali, Yunnan 671000, PR China.
J Control Release. 2018 Jan 28;270:290-303. doi: 10.1016/j.jconrel.2017.12.015. Epub 2017 Dec 19.
The blood-brain barrier (BBB) is one of the most essential protection mechanisms in the central nervous system (CNS). It selectively allows individual molecules such as small lipid-soluble molecules to pass through the capillary endothelial membrane while limiting the passage of pathogens or toxins. However, this protection mechanism is also a major obstacle during disease state since it dramatically hinders the drug delivery. In recent years, various tactics have been applied to assist drugs to cross the BBB including osmotic disruption of the BBB and chemical modification of prodrugs. Additionally, nanoparticles (NPs)-mediated drug delivery is emerging as an effective and non-invasive system to treat cerebral diseases. In this review, we will summarize and analyze the advances in the drug delivery across the BBB using various NPs in the last decade. The NPs will cover both traditional and novel nanocarriers. The traditional nanocarriers consist of poly(butylcyanoacrylate), poly(lactic-co-glycolic acid), poly(lactic acid) NPs, liposomes and inorganic systems. In the meanwhile, novel nanocarriers such as carbon quantum dots with their recent applications in drug delivery will also be introduced. In terms of significance, this review clearly depicts the BBB structure and comprehensively describes various NPs-mediated drug delivery systems according to different NPs species. Also, the BBB penetration mechanisms are concluded in general, emphasized and investigated in each drug delivery system.
血脑屏障(BBB)是中枢神经系统(CNS)中最重要的保护机制之一。它选择性地允许诸如小脂溶性分子等单个分子通过毛细血管内皮膜,同时限制病原体或毒素的通过。然而,这种保护机制在疾病状态下也是一个主要障碍,因为它极大地阻碍了药物的输送。近年来,已经应用了各种策略来帮助药物穿过 BBB,包括 BBB 的渗透破坏和前药的化学修饰。此外,纳米颗粒(NPs)介导的药物输送作为治疗脑部疾病的一种有效和非侵入性系统正在兴起。在这篇综述中,我们将总结和分析过去十年中使用各种 NPs 穿越 BBB 的药物输送的进展。NPs 将涵盖传统和新型纳米载体。传统的纳米载体包括聚(丁基氰基丙烯酸酯)、聚(乳酸-共-羟基乙酸)、聚乳酸 NPs、脂质体和无机系统。同时,还将介绍最近在药物输送中应用的新型纳米载体,如碳量子点。就意义而言,本综述清楚地描绘了 BBB 的结构,并根据不同的 NPs 种类全面描述了各种 NPs 介导的药物输送系统。此外,还总结了 BBB 穿透机制,并在每个药物输送系统中进行了强调和研究。