用于将DNA递送至骨骼肌的两亲性聚（四氢呋喃-b-环氧乙烷）共聚物的合成与评价
Synthesis and evaluation of amphiphilic poly(tetrahydrofuran-b-ethylene oxide) copolymers for DNA delivery into skeletal muscle.
作者信息
Pomel Catherine, Leborgne Christian, Cheradame Hervé, Scherman Daniel, Kichler Antoine, Guegan Philippe
机构信息
Laboratoire Matériaux Polymères aux Interfaces-UMR CNRS 7581, Université d'Evry, Evry, France.
出版信息
Pharm Res. 2008 Dec;25(12):2963-71. doi: 10.1007/s11095-008-9698-9. Epub 2008 Sep 3.
PURPOSE
Amphiphilic triblock copolymers such as the pluronic poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) L64 (pEO(13)-pPO(30)-pEO(13)) have been shown to mediate more efficient gene transfer in muscle as compared to naked DNA. We were interested in studying the effect of a chemical change of the central block of pluronic polymers on the transfection activity.
METHODS
We synthesized new amphiphilic copolymers in which the hydrophobic pPO block was replaced by poly(tetrahydrofuran) (pTHF) chains. The resulting triblock pEO-pTHF-pEO polymers have been characterized by NMR and SEC and assayed for in vitro and in vivo gene transfer.
RESULTS
The animal experiments showed that the new copolymers are able to significantly increase the transfection efficiency of plasmid DNA after intramuscular injection.
CONCLUSIONS
These results indicate that the capacity to enhance plasmid DNA transfection in skeletal muscle is not restricted to pEO-pPO-pEO arrangements.
目的
已表明两亲性三嵌段共聚物，如普朗尼克聚（环氧乙烷-嵌段-环氧丙烷-嵌段-环氧乙烷）L64（pEO(13)-pPO(30)-pEO(13)）与裸DNA相比，在肌肉中能介导更有效的基因转移。我们感兴趣的是研究普朗尼克聚合物中心嵌段的化学变化对转染活性的影响。
方法
我们合成了新的两亲性共聚物，其中疏水性的pPO嵌段被聚四氢呋喃（pTHF）链取代。所得的三嵌段pEO-pTHF-pEO聚合物已通过核磁共振和尺寸排阻色谱进行表征，并进行了体外和体内基因转移测定。
结果
动物实验表明，新的共聚物在肌肉注射后能够显著提高质粒DNA的转染效率。
结论
这些结果表明，增强骨骼肌中质粒DNA转染的能力并不局限于pEO-pPO-pEO结构。
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