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学科主题: 药学
题名:
Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals
作者: Qin, Yao3; Chen, Huali1; Zhang, Qianyu1; Wang, Xiaoxiao1; Yuan, Wenmin1; Kuai, Rui1; Tang, Jie1; Zhang, Li1; Zhang, Zhirong1; Zhang, Qiang4; Liu, Ji2; He, Qin1
关键词: TAT ; Cholesterol ; Doxorubicin ; Brain delivery ; Blood-brain barrier
刊名: INTERNATIONAL JOURNAL OF PHARMACEUTICS
发表日期: 2011-11-28
DOI: 10.1016/j.ijpharm.2011.09.008
卷: 420, 期:2, 页:304-312
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]: DRUG-DELIVERY ; HIV-1 TAT ; PROTEIN TRANSDUCTION ; PLASMA-MEMBRANE ; BREAST-CANCER ; TUMOR-MODEL ; DOXORUBICIN ; BARRIER ; NANOPARTICLES ; EFFICIENT
英文摘要:

The treatment of central nervous system diseases such as brain glioma is a major challenge due to the presence of the blood-brain barrier (BBB). A cell-penetrating peptide TAT (AYGRKKRRQRRR), which appears to enter cells with alacrity, was employed to enhance the delivery efficiency of normal drug formulation to the brain. Targeting liposomal formulations often apply modified phospholipids as anchors. However, cholesterol, another liposomal component more stable and cheaper, has not been fully investigated as an alternative anchor. In our study, TAT was covalently conjugated with cholesterol for preparing doxorubicin-loaded liposome for brain glioma therapy. Cellular uptake by brain capillary endothelial cells (BCECs) and C6 glioma cells was explored. The anti-proliferative activity against C6s confirmed strong inhibitory effect of the liposomes modified with doxorubicin-loaded TAT. The bio-distribution findings in brains and hearts were evident of higher efficiency of brain delivery and lower cardiotoxic risk. The results on survival of the brain glioma-bearing animals indicate that survival time of the glioma-bearing rats treated with TAT-modified liposome was much longer than in the other groups. In conclusion, the potency of the TAT-modified liposome to enter the BBB appears to be related with the TAT on the liposome′s surface. The TAT-modified liposome may improve the therapeutic efficacy on brain glioma in vitro and in vivo. (c) 2011 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 30873166 ; 81072599 ; 81130060 ; 2009CB903300
项目资助者: National Natural Science Foundation of China ; National Basic Research Program of China
WOS记录号: WOS:000303423800015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51073
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Taiji Grp, Chongqing Municipality 401147, Peoples R China
2.Sichuan Univ, W China Sch Pharmaceut, Key Lab Drug Targeting & Drug Delivery Syst, Chengdu Municipality 610041, Sichuan Provinc, Peoples R China
3.Sichuan Univ, W China Sch Preclin & Forens Med, Chengdu Municipality 610041, Sichuan Provinc, Peoples R China
4.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Qin, Yao,Chen, Huali,Zhang, Qianyu,et al. Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2011,420(2):304-312.
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