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学科主题: 药学
题名:
Chlorotoxin-modified stealth liposomes encapsulating levodopa for the targeting delivery against the Parkinson′s disease in the MPTP-induced mice model
作者: 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
发表日期: 2012
DOI: 10.3109/1061186X.2011.595490
卷: 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
所属项目编号: 2007CB935800 ; 2009CB930300 ; 2009ZX09310-001 ; 2007AA021811
项目资助者: National Basic Research Program of China ; State Key Projects ; 863 Project
WOS记录号: WOS:000297808300006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55374
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
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.
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