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Targeted Treatment of Choroidal Neovascularization Using Integrin-Mediated Sterically Stabilized Liposomes Loaded With Combretastatin A4
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
2009-06-01
DOI10.1089/jop.2008.0119
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
WOS记录号WOS:000266237100003
项目编号30430760
资助机构National Natural Science Foundation ; Peking University
引用统计
被引频次:12[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/400002259/55212
专题北京大学第三临床医学院_眼科
北京大学药学院_药剂学系
北京大学公共卫生学院_公共卫生学院
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
推荐引用方式
GB/T 7714
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.
APA Ma, Li.,Liu, Yu-Ling.,Ma, Zhi-Zhong.,Dou, Hong-Liang.,Xu, Jun-Hui.,...&Zhang, Qiang.(2009).Targeted Treatment of Choroidal Neovascularization Using Integrin-Mediated Sterically Stabilized Liposomes Loaded With Combretastatin A4.JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS,25(3),195-200.
MLA Ma, Li,et al."Targeted Treatment of Choroidal Neovascularization Using Integrin-Mediated Sterically Stabilized Liposomes Loaded With Combretastatin A4".JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS 25.3(2009):195-200.
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