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Chlorotoxin-modified stealth liposomes encapsulating levodopa for the targeting delivery against the Parkinson′s disease in the MPTP-induced mice model
Xiang, Yu; Wu, Qian; Liang, Liang; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Pu, Xiaoping; Zhang, Qiang
关键词Chlorotoxin Levodopa Liposomes Parkinson&Prime s Disease Targeted Drug Delivery
刊名JOURNAL OF DRUG TARGETING
2012
DOI10.3109/1061186X.2011.595490
20期:1页:67-75
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]BLOOD-BRAIN-BARRIER ; L-DOPA ; DOXORUBICIN ; DRUG ; TUMORS ; MOUSE ; PEPTIDE ; SYSTEM ; CELLS ; PATHOLOGY
英文摘要

Chlorotoxin (ClTx), originally isolated from scorpion venom of Leiurus quinquestriatus, is a 36-amino acid peptide and specifically binds to the brain gliomas and proliferating vascular endothelial cells. In this paper, it was first used to establish the ClTx-modified stealth liposomes (ClTx-LS) encapsulating levodopa (LD) for the targeting drug delivery against the Parkinson′s disease (PD). After the DSPE-PEG-ClTx was synthesized and identified, the ClTx-LS system was prepared and characterized. Its targeting capability was studied in vitro and in vivo, and finally its anti-PD activity was evaluated, with non-modified liposomes (LS) as control. It was demonstrated through flow cytometry and confocal microscopy that ClTx modification highly facilitated the uptake of LS by brain microvascular endothelial cells in vitro. After intraperitoneal injection to mice, the active targeting system loaded with LD significantly increased the distribution of dopamine and dihydroxyphenyl acetic acid, the metabolites of LD, in the substantia nigra and striata. In the methyl-phenyl-tetrahydropyridine (MPTP)-induced PD mice model, LD-loaded ClTx-LS significantly attenuated the serious behavioral disorders and diminished the MPTP-induced loss of tyrosine hydroxylase-positive dopaminergic neurons. In conclusion, ClTx-modified LS might serve as a targeting delivery system to transport more drugs into the brain for a better PD therapy.

语种英语
WOS记录号WOS:000297808300006
项目编号2007CB935800 ; 2009CB930300 ; 2009ZX09310-001 ; 2007AA021811
资助机构National Basic Research Program of China ; State Key Projects ; 863 Project
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55374
专题北京大学药学院
北京大学药学院_药剂学系
北京大学药学院_分子与细胞药理学系
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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Xiang, Yu,Wu, Qian,Liang, Liang,et al. Chlorotoxin-modified stealth liposomes encapsulating levodopa for the targeting delivery against the Parkinson′s disease in the MPTP-induced mice model[J]. JOURNAL OF DRUG TARGETING,2012,20(1):67-75.
APA Xiang, Yu.,Wu, Qian.,Liang, Liang.,Wang, Xueqing.,Wang, Jiancheng.,...&Zhang, Qiang.(2012).Chlorotoxin-modified stealth liposomes encapsulating levodopa for the targeting delivery against the Parkinson′s disease in the MPTP-induced mice model.JOURNAL OF DRUG TARGETING,20(1),67-75.
MLA Xiang, Yu,et al."Chlorotoxin-modified stealth liposomes encapsulating levodopa for the targeting delivery against the Parkinson′s disease in the MPTP-induced mice model".JOURNAL OF DRUG TARGETING 20.1(2012):67-75.
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