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Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals
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
2011-11-28
DOI10.1016/j.ijpharm.2011.09.008
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
WOS记录号WOS:000303423800015
项目编号30873166 ; 81072599 ; 81130060 ; 2009CB903300
资助机构National Natural Science Foundation of China ; National Basic Research Program of China
引用统计
被引频次:73[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/400002259/51073
专题北京大学药学院
北京大学药学院_药剂学系
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
推荐引用方式
GB/T 7714
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.
APA Qin, Yao.,Chen, Huali.,Zhang, Qianyu.,Wang, Xiaoxiao.,Yuan, Wenmin.,...&He, Qin.(2011).Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals.INTERNATIONAL JOURNAL OF PHARMACEUTICS,420(2),304-312.
MLA Qin, Yao,et al."Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals".INTERNATIONAL JOURNAL OF PHARMACEUTICS 420.2(2011):304-312.
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