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学科主题: 药学
题名:
Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting
作者: Xie, Fulan1; Yao, Nian1; Qin, Yao1; Zhang, Qianyu1; Chen, Huali1; Yuan, Mingqing1; Tang, Jie1; Li, Xiankun1; Fan, Wei1; Zhang, Qiang2; Wu, Yong1; Hai, Li1; He, Qin1
关键词: glucose ; polyethylene glycols ; liposome ; BBB ; brain-targeted
刊名: INTERNATIONAL JOURNAL OF NANOMEDICINE
发表日期: 2012
DOI: 10.2147/IJN.S23771
卷: 7, 页:163-175
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Nanoscience & Nanotechnology ; Pharmacology & Pharmacy
研究领域[WOS]: Science & Technology - Other Topics ; Pharmacology & Pharmacy
关键词[WOS]: IN-VIVO ; ENDOTHELIAL-CELLS ; BARRIER ; TRANSPORT ; DELIVERY ; DRUG ; NANOPARTICLES ; EXPRESSION ; VITRO ; CHOLESTEROL
英文摘要:

Background: An intimidating challenge to transporting drugs into the brain parenchyma is the presence of the blood-brain barrier (BBB). Glucose is an essential nutritional substance for brain function sustenance, which cannot be synthesized by the brain. Its transport primarily depends on the glucose transporters on the brain capillary endothelial cells. In this paper, the brain-targeted properties of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers were compared and evaluated to establish an optimized drug-delivery system.

Methods: Coumarin 6-loaded liposomes (GLU200-LIP, GLU400-LIP, GLU1000-LIP, and GLU2000-LIP) composed of phospholipids and glucose-derived cholesterols were prepared by thin-film dispersion-ultrasound method. The BBB model in vitro was developed to evaluate the transendothelial ability of the different liposomes crossing the BBB. The biodistribution of liposomes in the mice brains was identified by in vivo and ex vivo nearinfrared fluorescence imaging and confocal laser scanning microscopy and further analyzed quantitatively by high-performance liquid chromatography.

Results: Glucose-derived cholesterols were synthesized and identified, and coumarin 6-loaded liposomes were prepared successfully. The particle sizes of the four types of glucose-modified liposomes were around or smaller than 100 nm with a polydispersity index less than 0.300. GLU400-LIP, GLU1000-LIP, and GLU2000-LIP achieved higher cumulative cleared volumes on BBB model in vitro after 6 hours compared with GLU200-LIP (P < 0.05) and were significantly higher than that of the conventional liposome (P < 0.001). The qualitative and quantitative biodistribution results in the mice showed that the accumulation of GLU1000-LIP in the brain was the highest among all the groups (P < 0.01 versus LIP).

Conclusion: The data indicated that GLU400-LIP, GLU1000-LIP, and GLU2000-LIP all possess the potential of brain targeting, among which GLU1000-LIP, as a promising drug-delivery system, exhibited the strongest brain delivery capacity.

语种: 英语
所属项目编号: 81130060 ; 2009CB903300
项目资助者: State Key Program of National Natural Science of China ; National Basic Research Program
WOS记录号: WOS:000302701700001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51465
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Sichuan Univ, W China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Chengdu 610041, Sichuan, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China

Recommended Citation:
Xie, Fulan,Yao, Nian,Qin, Yao,et al. Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2012,7:163-175.
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