Oswald Mira, Geissler Simon, Goepferich Achim
Chemical & Pharmaceutical Development, Merck KGaA , Frankfurter Straße 250, 64293 Darmstadt, Germany.
Department for Pharmaceutical Technology, University of Regensburg , Universitätsstraße 31, 94030 Regensburg, Germany.
Mol Pharm. 2017 Jul 3;14(7):2177-2196. doi: 10.1021/acs.molpharmaceut.7b00158. Epub 2017 Jun 16.
The transport of drugs across the blood-brain barrier is challenging. The use of peptide sequences derived from viruses with a central nervous system (CNS) tropism is one elegant option. A prominent example is the rabies virus glycopeptide-29 (RVG-29), which is said to enable a targeted brain delivery. Although the entry mechanism of the rabies virus into the CNS is very well characterized, it is unknown whether RVG-29-functionalized drug delivery systems (DDSs) follow this pathway. RVG-29-functionalized DDSs present themselves with modifications of the RVG-29 peptide sequence and different physicochemical properties compared to the rabies virus. To our surprise, the impact of these changes on the functionality is completely neglected. This review explores virus-related CNS-targeting strategies by comparing RVG-29-functionalized DDSs with regard to their peptide modification, physiochemical properties and their behavior in cell culture studies with a special focus on the original pathway of rabies virus entry into the CNS.
药物穿过血脑屏障的运输具有挑战性。利用源自具有中枢神经系统（CNS）嗜性的病毒的肽序列是一种巧妙的选择。一个突出的例子是狂犬病病毒糖肽-29（RVG-29），据说它能够实现靶向脑递送。尽管狂犬病病毒进入中枢神经系统的机制已得到很好的表征，但尚不清楚RVG-29功能化药物递送系统（DDSs）是否遵循此途径。与狂犬病病毒相比，RVG-29功能化DDSs呈现出RVG-29肽序列的修饰和不同的物理化学性质。令我们惊讶的是，这些变化对功能的影响完全被忽视了。本综述通过比较RVG-29功能化DDSs在肽修饰、物理化学性质以及细胞培养研究中的行为，特别关注狂犬病病毒进入中枢神经系统的原始途径，探索与病毒相关的中枢神经系统靶向策略。
