药物输送
血脑屏障
PLGA公司
肽
体内
生物物理学
纳米颗粒
共轭体系
材料科学
化学
生物化学
中枢神经系统
纳米技术
生物
聚合物
生物技术
神经科学
复合材料
作者
Jingwei Li,Liang Feng,Li Fan,Yuan Zha,Le‐Hang Guo,Qizhi Zhang,Jun Chen,Zhiqing Pang,Yuchen Wang,Xinguo Jiang,Victor C. Yang,Longping Wen
出处
期刊:Biomaterials
[Elsevier]
日期:2011-07-01
卷期号:32 (21): 4943-4950
被引量:246
标识
DOI:10.1016/j.biomaterials.2011.03.031
摘要
The relative impermeability of the blood-brain barrier (BBB) results from tight junctions and efflux transport systems limits drug delivery to the central nervous system (CNS), and thus severely restricts the therapy of many central nervous system diseases. In order to enhance the brain-specific drug delivery, we employed a 12-mer phage display peptide library to isolate peptides that could target the drug delivery system to the brain. A 12-amino-acid-peptide (denoted as Pep TGN) which was displayed by bacteriophage Clone 12-2 was finally selected by rounds of in vivo screening. Pep TGN was covalently conjugated onto the surface of poly (ethyleneglycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) based nanoparticles (NPs). The cellular uptake of Pep TGN decorated nanoparticles was significantly higher than that of unmodified nanoparticles when incubated with bEnd.3 cells. Enhanced brain accumulation efficiency together with lower accumulation in liver and spleen was observed in the nude mice intravenously injected with Pep TGN conjugated nanoparticles compared with those injected with plain nanoparticles, showing powerful brain selectivity of Pep TGN. Coumarin 6 was used as a fluorescent probe for the evaluation of brain delivery properties. The brain Drug Targeting Index (DTI) of coumarin 6 incorporated in targeted nanoparticles was significantly higher than that of coumarin 6 incorporated in plain nanoparticles. In conclusion, the Pep TGN is a motif never been reported before and Pep TGN modified nanoparticles showed great potential in targeted drug delivery across the blood brain barrier.
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