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学科主题基础医学
PEG-conjugated PAMAM Dendrimers Mediate Efficient Intramuscular Gene Expression
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
2009-09-01
DOI10.1208/s12248-009-9116-1
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
WOS记录号WOS:000270544500001
项目编号30500197
资助机构National Natural Science Foundation of China
引用统计
被引频次:101[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/400002259/65848
专题北京大学基础医学院_心血管所
北京大学基础医学院
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
推荐引用方式
GB/T 7714
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.
APA Qi, Rong.,Gao, Yu.,Tang, Yin.,He, Rui-Rui.,Liu, Tao-Le.,...&Liu, George.(2009).PEG-conjugated PAMAM Dendrimers Mediate Efficient Intramuscular Gene Expression.AAPS JOURNAL,11(3),395-405.
MLA Qi, Rong,et al."PEG-conjugated PAMAM Dendrimers Mediate Efficient Intramuscular Gene Expression".AAPS JOURNAL 11.3(2009):395-405.
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