Journal
MOLECULAR PHARMACEUTICS
Volume 14, Issue 7, Pages 2177-2196Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00158
Keywords
CNS-targeting strategies; rabies virus glycopeptide; blood-brain barrier
Funding
- EU/EFPIA Innovative Medicines Initiative Joint Undertaking COMPACT [115363]
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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-fonctronalized 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.
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