Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle
Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle
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DOI：
10.1016/j.jconrel.2006.11.025
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发表时间：
2007-04-02
影响因子：
10.8
通讯作者：
Kim, Sung Wan
中科院分区：
文献类型：
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作者：
Chang, Chien-Wen;Choi, Donghoon;Kim, Sung Wan
基于裸质粒DNA（pDNA）的基因治疗具有低递送效率，并且因此具有低治疗效果。我们提出了一种可生物降解的非离子型三嵌段共聚物PEG（13）-PLGA（10）-PEG（13），以提高骨骼肌中的基因递送效率。通过原子力显微镜（AFM）成像、凝胶电泳和zeta电位分析，研究了PEG（13）PLGA（10）-PEG（13）对pDNA理化性质的影响。AFM成像表明，当它与聚合物混合时，pDNA的结构略微紧凑，而zeta电位测量表明带负电荷的pDNA的表面电位增加。PEG（13）-PLGA（10）-PEG（13）在骨骼肌细胞系中显示出与Pluronic P85相比相对较低的毒性。在0.25%聚合物溶液中递送的pDNA的荧光素酶表达比支化聚乙烯亚胺（bPEI（25 k））/pDNA高达三个数量级，并且在肌内施用后五天比裸pDNA高三倍。还观察到这种体内基因递送增强，显示出人血管内皮生长因子（VEGF）的两倍高表达。基于荧光标记的pDNA分布，推测PEG（13）-PLGA（10）-PEG（13）/pDNA与bPET（25 k）/pDNA相比更大的扩散性解释了体内更好的转染效率。综上所述，PEG（13）-PLGA（10）-PEG（13）与pDNA的组合具有提高骨骼肌中基因递送效率的潜力。(c)2006 Elsevier B. V.保留所有权利。
Naked plasmid DNA (pDNA)-based gene therapy has low delivery efficiency, and consequently, low therapeutic effect. We present a biodegradable nonionic triblock copolymer, PEG(13)-PLGA(10)-PEG(13), to enhance gene delivery efficiency in skeletal muscle. Effects of PEG(13)PLGA(10)-PEG(13) on physicochemical properties of pDNA were evaluated by atomic force microscopy (AFM) imaging, gel electrophoresis and zeta-potential analysis. AFM imaging suggested a slightly compacted structure of pDNA when it was mixed with the polymer, while zeta-potential measurement indicated an increased surface potential of negatively charged pDNA. PEG(13)-PLGA(10)-PEG(13) showed a relatively lower toxicity compared to Pluronic P85 in a skeletal muscle cell line. The luciferase expression of pDNA delivered in 0.25% polymer solution was up to three orders of magnitude more than branched polyethylenimine (bPEI(25 k))/pDNA and three times more than that of naked pDNA five days after intramuscular administration. This in vivo gene delivery enhancement was also observed displaying a two-fold higher expression of human vascular endothelial growth factor (VEGF). Based on fluorescence labeled pDNA distribution, it is speculated that the greater diffusivity of PEG(13)-PLGA(10)-PEG(13)/pDNA compared to bPET(25 k)/pDNA accounts for better transfection efficiency in vivo. To summarize, combining PEG(13)-PLGA(10)-PEG(13) with pDNA possesses the potential to improve gene delivery efficiency in skeletal muscle. (c) 2006 Elsevier B.V. All rights reserved.