A D‐Peptide Ligand of Nicotine Acetylcholine Receptors for Brain‐Targeted Drug Delivery |
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| Authors: | Xiaoli Wei Dr. Changyou Zhan Qing Shen Prof. Wei Fu Cao Xie Jie Gao Chunmei Peng Prof. Ping Zheng Prof. Weiyue Lu |
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| Affiliation: | 1. Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai, 201203 (P.R. China);2. State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200032 (P.R. China);3. State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433 (P.R. China) |
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| Abstract: | Lysosomes of brain capillary endothelial cells are implicated in nicotine acetylcholine receptor (nAChR)‐mediated transcytosis and act as an enzymatic barrier for the transport of peptide ligands to the brain. A D ‐peptide ligand of nAChRs (termed DCDX), which binds to nAChRs with an IC50 value of 84.5 nM , was developed by retro–inverso isomerization. DCDX displayed exceptional stability in lysosomal homogenate and serum, and demonstrated significantly higher transcytosis efficiency in an in vitro blood–brain barrier monolayer compared with the parent L ‐peptide. When modified on liposomal surface, DCDX facilitated significant brain‐targeted delivery of liposomes. As a result, brain‐targeted delivery of DCDX modified liposomes enhanced therapeutic efficiency of encapsulated doxorubicin for glioblastoma. This study illustrates the importance of ligand stability in nAChRs‐mediated transcytosis, and paves the way for developing stable brain‐targeted entities. |
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| Keywords: | blood– brain barrier D‐peptide ligands glioblastoma nicotine acetylcholine receptors |
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