Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
J Control Release. 2013 Oct 10;171(1):17-23. doi: 10.1016/j.jconrel.2013.06.028. Epub 2013 Jul 2.
The blood-brain barrier (BBB) prevents drugs' permeability into the brain and limits management of brain diseases. Specialized drug delivery systems (DDSs) are utterly required to overcome this barrier and to achieve efficient delivery of therapeutic agents to the brain. For this purpose, drug-encapsulating nanoparticles or vesicles, drug conjugates and other types of DDSs are being developed by many research groups worldwide. However, efficiency of the brain drug/DDS delivery and targeting is usually presented in indirect and vague form and it is hard to quantitatively estimate it based on the reported data. We searched for the scientific papers that were published in 1970-2012 that reported delivery of drugs or model compounds to the brain following systemic administration of DDSs via parenteral routes and contained quantitative data on brain drug/DDS delivery and targeting efficiency. We identified 123 publications that matched the search criteria and analyzed their experimental settings, formulation types, analytical methods, and the claimed efficiencies of drug/DDS brain targeting (brain/plasma or brain/tissue concentration ratios) and brain accumulation (% of the administered dose that accumulated in the brain). Based on the outcomes of this analysis, we describe the major research trends, discuss the efficiencies of the different drug/DDS brain targeting approaches, and provide recommendations for quantitative assessment of brain-targeting DDSs in the appropriately designed studies.
血脑屏障（BBB）阻止药物渗透到大脑中，并限制了脑部疾病的治疗。需要专门的药物传递系统（DDS）来克服这一障碍，实现治疗剂向大脑的有效传递。为此，许多研究小组正在开发药物包封的纳米颗粒或囊泡、药物偶联物和其他类型的 DDS。然而，脑内药物/DDS 传递和靶向的效率通常以间接和模糊的形式呈现，并且很难根据报告的数据进行定量估计。我们搜索了 1970 年至 2012 年期间发表的科学论文，这些论文报告了通过肠外途径给予 DDS 后，药物或模型化合物向大脑的传递，并包含关于脑内药物/DDS 传递和靶向效率的定量数据。我们确定了 123 篇符合搜索标准的出版物，并分析了它们的实验设置、制剂类型、分析方法以及声称的药物/DDS 脑靶向效率（脑/血浆或脑/组织浓度比）和脑蓄积（累积在脑中的给药剂量的百分比）。基于该分析的结果，我们描述了主要的研究趋势，讨论了不同的药物/DDS 脑靶向方法的效率，并为在适当设计的研究中定量评估脑靶向 DDS 提供了建议。
