PEG-conjugated PAMAM Dendrimers Mediate Efficient Intramuscular Gene Expression

被引:0
|
作者
Rong Qi
Yu Gao
Yin Tang
Rui-Rui He
Tao-Le Liu
Yun He
Sheng Sun
Bo-Yu Li
Yang-Bing Li
George Liu
机构
[1] Peking University Health Science Center,Peking University Institute of Cardiovascular Sciences
[2] Peking University,School of Pharmacy, Peking University Health Science Center
[3] Peking University,Key Laboratory of Molecular Cardiovascular Sciences
[4] Ministry of Education,undefined
来源
The AAPS Journal | 2009年 / 11卷
关键词
intramuscular gene delivery; PAMAM dendrimer; PEG conjugation; toxicity;
D O I
暂无
中图分类号
学科分类号
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.
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页码:395 / 405
页数:10
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