可生物降解材料作为基因载体的研究  

Investigation of Biodegradable Materials as Polymeric Gene Carriers

作　　者：杨远[1] 贾文祥[1] 祁欣[1] 曾蔚[1] 杨发龙[1] 谢轶[1] 杨维青[1] 张再容[1] 周绍兵[2] 李孝红[2] 

机构地区：[1]四川大学华西基础医学与法医学院微生物学教研室,成都610041 [2]中国科学院成都有机化学所高分子材料室

出　　处：《生物医学工程学杂志》2006年第3期573-577,共5页Journal of Biomedical Engineering

基　　金：国家自然科学基金;973基金资助项目(50303018;29774034)

摘　　要：研究可生物降解聚合物作为控制释放的基因载体。合成聚乳酸-聚乙二醇二元共聚物（Poly（Dl-lactic acid）-co—poly（ethylene glycol，PELA）及聚乳酸-聚乙二醇-聚乙醇酸三元无规共聚物（Poly（lactic acid）-co—poly（ethylene glycol）-co—poly（glycolic acid）random copolymer，PLGAE），包裹质粒pCH110。探讨了PELA和PLGAE作为基因载体包裹DNA的各种影响因素，这两种控制释放体系的体外降解及释放行为以及对它们的细胞毒性及体外转染效率进行了测定。制备的PELA微球平均粒径1～3μm，包裹效率为62％。PLGAE微球平均粒径0．72μm，包裹效率为70％。采用包裹了质粒pCH110的微球对COS-1细胞的细胞毒性及转染实验中得出：二者的细胞毒性较小，PELA和PLGAE的转染效率均较高，且能持续表达96h，其中PLGAE的缓释效果更明显。可生物降解聚合物材料作为基因载体具有较强的优越性。This is a study on the biodegradable polymers as gene controlled-released coatings for gene transfer. The PELA （poly （Dl-lactic acid）-co-poly （ethylene glycol）, and PLGAE （poly （lactic acid）-co-poly （ethylene glycol）-co-poly （glycolic acid） random copolymer） were synthesized and prepared as the coatings of plasmid pCH110 in the transfection. All kinds of factors affecting the loading efficiency, cytotoxicity, transfection efficiency and the course of the degradation and release in vitro were discussed. The average diameters of microspheres of PELA and PLGAE were 1-3 μm and 0.72 μm respectively. The loading efficiency levels of them were 62% and 70% respectively. The transfection efficiency levels of two kinds of pCH110 delivery system for COS-1 cells were higher and two of them had few cytotoxicity. After transfection, the X-gal assay was performed and reported positive for 96 h. The biodegradable polymeric materials as gene carriers possess their potential superiority.

关 键 词：可生物降解聚合物 基因载体 微球 转染 

分 类 号：R318.08[医药卫生—生物医学工程] R394[医药卫生—基础医学]