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目的:本文旨在制备叶酸(folate,FA)修饰的纳米结构脂质载体(FA-NLC)作为基因药物(p DNA)传递载体,并研究FA-NLC/p DNA的药剂学和生物学特性。方法:通过FA与DSPE-PEG2000-NH2发生酰胺反应生成FA-PEG2000-DSPE;采用熔融乳化法制备阳离子NLC,与p DNA复合,制备NLC/p DNA;以合成的FA-PEG2000-DSPE对NLC/p DNA进行表面修饰,制得FA-NLC/p DNA。本研究对NLC的体外相关性质进行了初步评价,并对粒径、Zeta电位、包封率、体外细胞毒性及细胞转染效率等方面与市售Lipofectamin3000进行了对比。结果:FA-NLC/p DNA平均粒径为(143.8±5.1)nm,多聚分散度(PDI)为(0.19±0.04),Zeta电位为(12.1±2.9)m V,p DNA结合率为(90.6±2.7)%;FA-NLC/p DNA组60 h基因的累积释放率为80%,较NLC/p DNA组及Lipofectamin3000组释放更为缓慢;48 h的细胞转染率显著强于NLC/p DNA组和Lipofectamin3000组,且无明显细胞毒性。结论:上述结果表明,FA-NLC有潜力成为高效低毒的非病毒型基因药物传递载体。
OBJECTIVE: The purpose of this study was to prepare the folate (FA) modified nanostructured lipid vector (FA-NLC) as a gene delivery vector for p DNA and to study the pharmacological and biological properties of FA-NLC / p DNA. METHODS: FA-PEG2000-DSPE was produced by the amide reaction between FA and DSPE-PEG2000-NH2. Cationic NLC was prepared by melt emulsification and complexed with p DNA to prepare NLC / p DNA. p DNA surface modification to prepare FA-NLC / p DNA. In this study, the in vitro correlation of NLC was preliminarily evaluated, and the particle size, Zeta potential, entrapment efficiency, cytotoxicity in vitro and transfection efficiency of cells were compared with the commercially available Lipofectamin3000. RESULTS: The average particle size of FA-NLC / p DNA was (143.8 ± 5.1) nm, the PDI was (0.19 ± 0.04) and the Zeta potential was (12.1 ± 2.9) 90.6 ± 2.7)%. The cumulative release rate of 60 h gene in FA-NLC / p DNA group was 80%, which was slower than that in NLC / p DNA group and Lipofectamin3000 group. NLC / p DNA group and Lipofectamin 3000 group, and no obvious cytotoxicity. CONCLUSIONS: The above results indicate that FA-NLC has the potential to be a highly efficient and low toxic non-viral gene delivery carrier.