Intrathecal drug delivery in the era of nanomedicine.,Advanced Drug Delivery Reviews

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Intrathecal drug delivery in the era of nanomedicine.
Advanced Drug Delivery Reviews ( IF 15.2 ) Pub Date : 2020-03-03 , DOI: 10.1016/j.addr.2020.02.006
M J Fowler ₁ , J D Cotter ₁ , B E Knight ₁ , E M Sevick-Muraca ₂ , D I Sandberg ₃ , R W Sirianni ₁

Affiliation

Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.

中文翻译：

纳米医学时代的鞘内给药。

将物质直接注入围绕大脑和脊髓的脑脊液 (CSF) 是一种可以绕过血脑屏障以将药物输送到中枢神经系统 (CNS) 的方法。然而，通过鞘内注射给药的分子，包括脑室内、脑池内或腰椎位置，在蛛网膜下腔内遇到新的障碍。这些障碍包括脑脊液清除时相对较高的周转率以及对组织或细胞靶标的潜在不充分递送。纳米医学可以提供解决方案。与自由给药的命运相反，纳米医学系统可以在蛛网膜下腔中导航，以维持治疗分子、基因和成像剂在中枢神经系统内的输送。一些证据表明，某些纳米药物可以在鞘内给药后到达实质。在这里，我们将讨论鞘内纳米药物的临床前和临床应用，包括纳米颗粒、微粒、树枝状聚合物、胶束、脂质体、复合物和其他可改变组织中分子分布的胶体材料。我们的审查形成了对药物输送到脑脊液的基本理解，可以在此基础上更好地设计用于鞘内治疗疾病的纳米医学。和其他可改变组织中分子分布的胶体材料。我们的审查形成了对药物输送到脑脊液的基本理解，可以在此基础上更好地设计用于鞘内治疗疾病的纳米医学。和其他可改变组织中分子分布的胶体材料。我们的审查形成了对药物输送到脑脊液的基本理解，可以在此基础上更好地设计用于鞘内治疗疾病的纳米医学。

更新日期：2020-04-20

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