Exploiting BBB disruption for the delivery of nanocarriers to the diseased CNS.
Exploiting BBB disruption for the delivery of nanocarriers to the diseased CNS.
复制标题
DOI：
10.1016/j.copbio.2019.01.013
复制
发表时间：
2019-12
影响因子：
7.7
通讯作者：
Benjamin J. Umlauf;E. Shusta
中科院分区：
文献类型：
--
作者：
Benjamin J. Umlauf;E. Shusta
血脑屏障（BBB）由脑内皮细胞形成，并使用专门的物理、运输和代谢特性将血液成分与中枢神经系统（CNS）隔离[1]。虽然小的亲脂性分子的子集可以容易地扩散通过BBB，但是对于治疗CNS病症可能非常期望的核酸、肽、蛋白质和纳米颗粒治疗剂不能直接进入CNS。因此，正在研究几种绕过BBB以递送治疗剂的策略，包括利用受体介导的机制通过脑内皮细胞转胞吞[2]，在CNS内植入治疗材料[3]，通过鼻内和鞘内途径施用治疗剂[4]等[5]。这些策略已在文献[2，4，5，6，7]的其他地方进行了综述。在这篇综述中，我们将重点关注新兴的方法，利用病理或诱导的血脑屏障disruption.Additionally靶向治疗CNS，这篇综述选择性地侧重于治疗应用，采用nanocarrier货物交付。纳米载体作为治疗CNS疾病的药物递送平台特别令人感兴趣。这类颗粒，包括但不限于纳米颗粒和脂质体，与未缀合的小分子和治疗性蛋白质相比具有有益的性质。这些包括采用表面改性的能力，这些表面改性可以驱动期望的CNS渗透，增强药代动力学特性，以及靶向特异性细胞或结构[8]。此外，纳米载体携带浓缩的小分子和治疗性蛋白质有效载荷，其导致药物在靶位点的累积增加，以及治疗性有效载荷的受控释放以减少脱靶不良事件[9，10]。
The blood–brain barrier (BBB) is formed by brain endothelial cells and segregates blood components from the central nervous system (CNS) using specialized physical, transport, and metabolic properties [1]. While a subset of small, lipophilic molecules can diffuse readily through the BBB, nucleic acid, peptide, protein, and nanoparticulate therapeutics that could be highly desirable for treating CNS disorders cannot directly access the CNS. As such, several strategies to circumvent the BBB to deliver therapeutics are being investigated including utilizing receptor-mediated machinery to transcytose through brain endothelial cells [2], implanting therapeutic materials within the CNS [3], administering therapeutics by intranasal and intrathecal routes [4], among others [5]. These strategies have been reviewed elsewhere in the literature [2, 4, 5, 6, 7]. In this review, we will instead focus on emerging approaches to target therapeutics to the CNS that exploit pathologic or induced BBB disruption.Additionally, this review selectively focuses on therapeutic applications that employ nanocarriers for cargo delivery. Nanocarriers are of particular interest as a drug delivery platform to treat CNS disease. This class of particles, including but not limited to nanoparticles and liposomes, have beneficial properties compared to unconjugated small molecules and therapeutic proteins. These include the ability to employ surface modifications that can drive desirable CNS penetration, enhance pharmacokinetic properties, and target-specific cells or structures [8]. Additionally, nanocarriers carry concentrated small molecule and therapeutic protein payloads that result in increased accumulation of drug at the target site, as well as controlled release of therapeutic payload to reduce off target adverse events [9, 10].