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学科主题: 基础医学
题名:
PEG-conjugated PAMAM Dendrimers Mediate Efficient Intramuscular Gene Expression
作者: Qi, Rong1,3; Gao, Yu2; Tang, Yin1,3; He, Rui-Rui2; Liu, Tao-Le2; He, Yun2; Sun, Sheng2; Li, Bo-Yu2; Li, Yang-Bing2; Liu, George1,3
关键词: intramuscular gene delivery ; PAMAM dendrimer ; PEG conjugation ; toxicity
刊名: AAPS JOURNAL
发表日期: 2009-09-01
DOI: 10.1208/s12248-009-9116-1
卷: 11, 期:3, 页:395-405
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]: IN-VIVO ; POLYAMIDOAMINE DENDRIMERS ; SKELETAL-MUSCLE ; DRUG-DELIVERY ; POLYMER STRUCTURE ; DNA DELIVERY ; CELLS ; VITRO ; CYTOTOXICITY ; COPOLYMERS
英文摘要:

Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity and unsatisfied in vivo efficacy limit their applications. In this study, to improve their characteristics as gene delivery carriers, polyethylene glycol (PEG, molecular weight 5,000) was conjugated to G5 and G6 PAMAM dendrimers (PEG-PAMAM) at three different molar ratios of 4%, 8%, and 15% (PEG to surface amine per PAMAM dendrimer molecular). Compared with unconjugated PAMAM dendrimers, PEG conjugation significantly decreased the in vitro and in vivo cytotoxicities and hemolysis of G5 and G6 dendrimers, especially at higher PEG molar ratios. Among all of the PEG-PAMAM dendrimers, 8% PEG-conjugated G5 and G6 dendrimers (G5-8% PEG, G6-8% PEG) resulted in the most efficient muscular gene expression when polyplexes were injected intramuscularly to the quadriceps of neonatal mice. Consistent with the in vivo results, these two 8% PEG-conjugated PAMAM dendrimers could also mediate the highest in vitro transfection in 293A cells. Therefore, G5-8% PEG and G6-8% PEG possess a great potential for gene delivery both in vivo and in vitro.

语种: 英语
所属项目编号: 30500197
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000270544500001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65848
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100083, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Pharm, Beijing 100083, Peoples R China

Recommended Citation:
Qi, Rong,Gao, Yu,Tang, Yin,et al. PEG-conjugated PAMAM Dendrimers Mediate Efficient Intramuscular Gene Expression[J]. AAPS JOURNAL,2009,11(3):395-405.
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