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学科主题: 药学
题名:
Comparative study of the in vitro and in vivo characteristics of cationic and neutral liposomes
作者: Zhao, Wei; Zhuang, Song; Qi, Xian-Rong
关键词: cationic liposomes ; PEGylation ; electrostatic interaction ; aggregation ; anticancer efficacy ; biodistribution
刊名: INTERNATIONAL JOURNAL OF NANOMEDICINE
发表日期: 2011
DOI: 10.2147/IJN.S25399
卷: 6, 页:3087-3098
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]: POLY(ETHYLENE GLYCOL) LIPOSOMES ; SOYBEAN-DERIVED STEROLS ; ENDOTHELIAL-CELLS ; DRUG-DELIVERY ; MICE ; DOXORUBICIN ; SURFACE ; SERUM ; PHARMACOKINETICS ; TRANSFECTION
英文摘要:

Neutral liposomes (NLP) exhibit preferential localization in solid tumors based on the enhanced permeation and retention (EPR) effect. Cationic liposomes (CLP) have a propensity for localizing in newly formed tumor vessels and they have a potentially enhanced antitumor effect. However, an increased amount of cationic lipids in liposomes also induces aggregation through electrostatic interactions between the liposomes and the anionic species in the circulation, which results in a reduced EPR effect. Consequently, it is important to investigate the characteristics of liposomes with different surface potentials in vitro to achieve an optimal intratumoral distribution and antitumor effect in vivo. In this study, the authors evaluated the characteristics of doxorubicin (DOX)-loaded NLPs, CLPs, polyethylene glycol (PEG)-modified NLPs (NLP-PEG), and PEGylated CLPs (CLP-PEG) (ie, encapsulation efficacy, zeta potential, size, membrane fluidity, aggregation in serum, and uptake of liposomes into rat aortic endothelial cells (RAECs)) to further understand their influences on the pharmacokinetics, biodistribution, and antitumor therapy in vivo. The results showed that increased amounts of cationic lipids resulted in severe liposome aggregation in the presence of serum, yet it did not alter the membrane fluidity to a large extent. The uptake of liposomes into RAECs, visualized by confocal fluorescence microscopy, confirmed the rapid uptake of CLP by the endothelial cells compared with NLP. However, the pharmacokinetics, biodistribution and anticancer efficacies of these liposomes in vivo revealed that the CLP with highly positive surface potentials exhibited reduced circulation times and poor distribution in tumors. The NLP-PEG exhibited the highest anticancer efficacy; CLP-PEG, the second highest; and CLP with the most positive surface potential, the lowest. These phenomena were mostly due to the rapid aggregation in serum and subsequent accumulation in the lungs upon the intravenous injection of the CLP. Caution should be exercised when chemotherapeutic drugs are loaded into CLP for tumor therapy.

语种: 英语
所属项目编号: 30772665 ; 30970785 ; 20100001110056
项目资助者: National Natural Science Foundation of China ; Doctoral Foundation of the Ministry of Education of China
WOS记录号: WOS:000297691800001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54830
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: Peking Univ, Dept Pharmaceut, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Zhao, Wei,Zhuang, Song,Qi, Xian-Rong. Comparative study of the in vitro and in vivo characteristics of cationic and neutral liposomes[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2011,6:3087-3098.
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