【作者】 马昆； 胡敏新； 汪卫军； 齐岩； 邹积宏； 邱利焱； 金一；

【Author】 MA Kun1,WANG Wei–jun2, HU Min–Xin1, QI Yan3, QIU Li–Yan1, JIN Yi 1*(1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; 2 Zhejiang Xianju Pharmaceutical Co.,Ltd. Xianju, Zhejiang 317300, China; 3College of life Sciences, Heilung–kiang University, Harbin 150080, China)

【机构】 浙江大学药学院药物制剂剂研究所； 浙江仙琚制药股份有限公司； 黑龙江大学生命科学院；

【摘要】 目的将曲安奈德接枝低分子量聚乙烯亚胺(PEI1800)合成新型非病毒基因载体TA-PEI,提高转染效率,降低毒性。方法曲安奈德的21位羟基用甲磺酰氯取代,生成曲安奈德甲磺酸酯。PEI1800,Traut’s试剂与曲安奈德甲磺酸酯一步反应生成TA-PEI聚合物。将TA-PEI与pDNA复合生成polyplex,其理化性质,转染效率和细胞毒性被研究。结果TA-PEI被合成。其缓冲能力与PEI25K相似,优于纯水。其能与pDNA复合形成200nm左右的粒子。转染活性提高,优于PEI25K,细胞毒性低于PEI25K。结论接枝TA后,PEI1800的转基因活性增强,而毒性较低,是一种有希望用于基因治疗的基因载体。更多还原

【Abstract】 OBJECTIVE Triamcinolone acetonide (TA) was conjugated with low molecular weights PEI (PEI1800) to synthesize a novel non–viral carrier (TA–PEI) to enhance its transfection efficiency and reduce cytotoxicity. METHODS TA with 21-OH was reacted with methanesulfonyl chloride to create TA mesylate. Then a one-pot reaction between PEI 1800, Traut’s reagent and TA mesylate yielded TA-PEI polymer. And the polyplex of TA-PEI/pDNA was prepared. Its physicochemical characteristics, transfection efficiency and cytotoxicity were investigated. RESULTS TA–PEI was synthesized. Its buffer capacity was similar to PEI 25K and better than pure water. It could complex with pDNA to form particle around 200 nm. Its transfection activity was enhanced and higher than that of PEI 25K. Its cytotoxicity was lower than that of PEI 25K. CONCLUSION After conjugated with TA, transgenic activity of PEI 1800 was improved and with low cytotoxicity. TA–PEI has a great potential for gene therapy as non–viral carrier.更多还原