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目的制备p H-敏感、电荷翻转型聚苹果酸纳米接枝物(多柔比星聚苹果酸-聚乙烯亚胺-2,3-二甲基马来酸酐,DOX/PMLA-PEI-DMA),研究其电荷翻转特性、体外释药、细胞内摄作用以及体外细胞毒性。方法以L-天冬氨酸为原料合成β-聚苹果酸,将聚乙烯亚胺、多柔比星以酰胺键连接到β-聚苹果酸骨架上,电荷保护基团2,3-二甲基马来酸酐通过羟基乙胺连接到β-聚苹果酸上,制备得到纳米接枝物多柔比星聚苹果酸-聚乙烯亚胺-2,3-二甲基马来酸酐。核磁共振光谱表征β-聚苹果酸及纳米接枝物的结构,动态透析法模拟体外释药特性,贝克曼粒度分析仪测定不同p H条件下纳米接枝物的Zeta电位,采用Huh7细胞研究纳米接枝物的内摄作用和细胞毒性。结果成功制备药物载体β-聚苹果酸和纳米接枝物多柔比星聚苹果酸-聚乙烯亚胺-2,3-二甲基马来酸酐;证实多柔比星聚苹果酸-聚乙烯亚胺-2,3-二甲基马来酸酐具有p H-敏感、电荷翻转特性,且其药物的释放具有p H依赖性;多柔比星聚苹果酸-聚乙烯亚胺-2,3-二甲基马来酸酐能够有效地提高多柔比星的细胞内摄作用,细胞毒性实验证实其具有很好的抗肿瘤能力。结论纳米接枝物多柔比星聚苹果酸-聚乙烯亚胺-2,3-二甲基马来酸酐是一种潜在的p H响应型靶向给药体系。
OBJECTIVE To prepare pH- sensitive, charge-inversion type polymalic acid nanocomposite (doxorubicin polymalic acid-polyethyleneimine-2,3-dimethyl maleic anhydride, DOX / PMLA-PEI-DMA) , Studied its charge inversion properties, in vitro release, intracellular effects and in vitro cytotoxicity. Methods β-polymalic acid was synthesized from L-aspartic acid, polyethyleneimine and doxorubicin were connected to β-polymalic acid by amide bond, and the charge-protecting group 2,3-dimethyl The maleic anhydride is connected to the β-polymalic acid through hydroxyethylamine to prepare the nano-grafted doxorubicin poly-malic acid-polyethyleneimine-2,3-dimethyl maleic anhydride. Nuclear magnetic resonance spectroscopy was used to characterize the structure of β-polymalic acid and nanocomposite. Dynamic dialysis was used to simulate the drug release in vitro. The Zeta potential of nanografted material under different p H was determined by Beckman particle size analyzer. Graft endocytosis and cytotoxicity. Results The drug carrier β-polymalic acid and nano-grafted doxorubicin poly-malic acid-polyethyleneimine-2,3-dimethyl maleic anhydride were successfully prepared. The results showed that doxorubicin poly-malic acid-polyethylene Imine-2,3-dimethyl maleic anhydride has p H-sensitive, charge-reversal properties and its drug release has a p H -dependency; doxorubicin polymalic acid-polyethyleneimine-2,3 - Dimethyl maleic anhydride can effectively improve the intracellular uptake of doxorubicin, cytotoxicity experiments confirmed its good anti-tumor ability. Conclusion The nano-grafted doxorubicin poly-malic acid-polyethyleneimine-2,3-dimethyl maleic anhydride is a potential p H-responsive target delivery system.