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利用壳聚糖制备了不同N/P(氮/磷)物质的量比的壳聚糖/基因传递系统。通过凝胶电泳、激光粒度分析和原子力显微分析技术研究了壳聚糖分子量、N/P物质的量比对传递系统结合性能、平均粒径、Zeta-电位和颗粒形貌的影响;通过体外模拟考察了传递系统的抗消化的能力和控释行为。结果显示,壳聚糖分子量越大、N/P物质的量比越大,对基因的保护能力越强,形成的传递系统在模拟环境中越稳定,抗DNaseⅠ和溶菌酶消化的能力越强。pH值的降低使壳聚糖显示出"质子海绵"效应,pH值增大使传递系统结构松散,导致基因的释放。

A polymer conjugate was synthesized by the reaction between aldehyde group of aldehyded chitosan(CS-CHO) and amino group of polyethylenimine(PEI) to formulate the low toxicity,certain effect gene vector.Aldehyde degree of the CS-CHO is 29.6%,and the structure was characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance.The effects of feed ratio of CS-CHO and PEI of 600g/mol,the feeding order on the grafting degree were investigated.The experimental results show that the grafting degree increases with the increase of the amount of PEI.When the feed ratio of the CS-CHO and PEI is less than 2∶1,the maximum geafting is 41.87%.When more PEI is added,the grafting ratio will reduce to 26.98%.The effect of feeding order on the grafting degree is relatively small.When the feed ratio of the CS-CHO and PEI is 2∶1,the maximum grafting degree is 29.21% by directly mixing CS-CHO and PEI.

参考文献

[1] De Laporte L;Rea JC;Shea LD .Design of modular non-viral gene therapy vectors[J].Biomaterials,2006(7):947-954.
[2] Han J;Il Yeom-Y .Specific gene transfer mediated by galactosylated poly-L-lysine into hepatoma cells.[J].International Journal of Pharmaceutics,2000(1/2):151-160.
[3] 贺灵芝,曾庆友,许瑞安.基因治疗中高分子载体的发展现状[J].高分子通报,2010(10):46-52.
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