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学科主题: 临床医学
题名:
Targeted Treatment of Choroidal Neovascularization Using Integrin-Mediated Sterically Stabilized Liposomes Loaded With Combretastatin A4
作者: Ma, Li; Liu, Yu-Ling1; Ma, Zhi-Zhong; Dou, Hong-Liang; Xu, Jun-Hui2; Wang, Jian-Cheng2; Zhang, Xuan2; Zhang, Qiang2
刊名: JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
发表日期: 2009-06-01
DOI: 10.1089/jop.2008.0119
卷: 25, 期:3, 页:195-200
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Ophthalmology ; Pharmacology & Pharmacy
研究领域[WOS]: Ophthalmology ; Pharmacology & Pharmacy
关键词[WOS]: A-4 PRODRUG ; IN-VIVO ; PHOSPHATE ; AGENT ; DOXORUBICIN ; DELIVERY ; GROWTH ; TUMORS
英文摘要:

Purpose: The objective of this study was to develop an efficient vasculature-targeted liposomal combretastatin A4 (CA4), by the modification of the sterically stabilized liposomes (SSL) with a ligand of integrins and to explore the possibility of such system for the treatment of choroidal neovascularization (CNV).

Methods: CA4-loaded liposomes were prepared by thin-film dispersion method. The linear arginine-glycine-aspartic acid tripeptide (RGD) with affinity for integrins such as alpha v beta 3 expressed on rapidly proliferative vascular endothelial cells was coupled to the distal end of polyethylene glycol (PEG) connected on the surface of SSL. The liposome delivery system was characterized in terms of size and size distribution profiles by dynamic light scattering method, entrapment efficiency, and leakage properties by high-performance liquid chromatography (HPLC). The uptake efficiency by human umbilical vein endothelial cells (HUVECs) was evaluated by confocal microscopy. The therapeutic efficacy was quantitatively assessed by choroidal flat mounts.

Results: CA4-loaded RGD-SSL (RGD-SSL-CA4) was obtained with an entrapment efficiency over 70% and an average diameter of similar to 120 nm. The leakage property of RGD-SSL-CA4 was similar with SSL-CA4, both were slower than CA4 ethanol solution. Confocal microscopy studies revealed that RGD-SSL could facilitate the liposomes′ uptake into HUVECs. Rats treated with two intravenous injections of 7 mg/kg RGD-SSL-CA4 resulted in a significant reduction in the area of CNV compared with control group (P < 0.05).

Conclusions: RGD-modified SSL loaded with CA4 can be successfully prepared, and the vasculature-targeted liposome system would increase the uptake of HUVECs and improve the therapeutic efficacy of CA4 on CNV compared with the control formulations.

语种: 英语
所属项目编号: 30430760
项目资助者: National Natural Science Foundation ; Peking University
WOS记录号: WOS:000266237100003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55212
Appears in Collections:北京大学第三临床医学院_眼科_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Ctr Eye, Dept Ophthalmol, Beijing 100083, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100083, Peoples R China

Recommended Citation:
Ma, Li,Liu, Yu-Ling,Ma, Zhi-Zhong,et al. Targeted Treatment of Choroidal Neovascularization Using Integrin-Mediated Sterically Stabilized Liposomes Loaded With Combretastatin A4[J]. JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS,2009,25(3):195-200.
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