A novel chitosan oligosaccharide-stearic acid micelles for gene delivery: Properties and in vitro transfection studies
A novel chitosan oligosaccharide-stearic acid micelles for gene delivery: Properties and in vitro transfection studies
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DOI：
10.1016/j.ijpharm.2006.02.026
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发表时间：
2006-06-06
影响因子：
5.8
通讯作者：
Zeng, Su
中科院分区：
文献类型：
--
作者：
Hu, Fu-Qiang;Zhao, Meng-Dan;Zeng, Su
通过1-乙基-3-(3-二甲氨基丙基)碳二亚胺(EDC)介导的偶联反应合成了硬脂酸(SA)接枝壳低聚糖(CSO-SA)，证明了CSO-SA在水溶液中自聚集形成胶束状结构。氨基取代度为15.4%的CSO-SA的临界胶束浓度为0.035 mg/ml，当CSO-SA浓度为1 mg/ml时，胶束的体积平均流体直径为70.6 nm，粒径分布较窄，表面电位为46.4+/-0.1 mV。由于胶束的阳离子性质，胶束可以将DNA胶束紧密结合形成胶束/DNA复合物纳米颗粒，从而有效地保护凝聚的DNA免受DNase1的酶降解。当N/P比从0.25增加到3.6和从3.6增加到58时，CSO-SA胶束/DNA复合体的体积平均流体直径从203 nm增加到318 nm，并由于Zeta电位的变化而减小到102 mm。CSO-SA胶束对A549细胞的IC50值为543.16微克/毫升，而脂质体的IC50值约为6微克/毫升。CSO-SA/DNA(N/P比为29)的转染率随转染时间的延长(76 H)而提高，而脂质体(TM)2000/DNA的转染率在24 h达到最佳，10%胎牛血清对CSO-SA的转染率无明显影响，表现出明显的促进作用。CSO-SA胶束在A549细胞中的最佳转染率约为15%，高于CSO的约2%，接近脂质体(TM)2000的约20%。低细胞毒性、可生物降解的CSO-SA胶束可作为一种有效的DNA凝聚载体用于基因传递系统。(C)2006爱思唯尔B.V.保留所有权利。
Stearic acid (SA) grafted chitosan oligosaccharide (CSO) (CSO-SA), which was synthesized by an 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-mediated coupling reaction, was demonstrated to form micelle like structure by self-aggregation in aqueous solution. The critical micelle concentration (CMC) of CSO-SA with 15.4% amino substituted degree of CSO was about 0.035 mg/ml. The micelles with I mg/ml CSO-SA concentration had 70.6 nm volume average hydrodynamic diameter with a narrow size distribution and 46.4 +/- 0.1 mV surface potential. Due to the cationic property, the micelles could compact the plasmid DNA to form micelle/DNA complexes nanoparticles, which can efficiently protect the condensed DNA from enzymatic degradation by DNase 1. The volume average hydrodynamic diameter of CSO-SA micelle/DNA complex increased from 203 nm to 318 nm and decreased to 102 mm due to the variation of zeta potential when the N/P ratio increased from 0.25 to 3.6 and from 3.6 to 58. The IC50 value of the CSO-SA micelle against A549 cells was 543.16 mu g/ml, while the IC50 of Lipofectamine (TM) 2000 was about 6 mu g/ml. The in vitro transfection efficiency of CSO-SA micelles was investigated by using plasmid DNA (pEGFP-C1). The transfection efficiency with CSO-SA/DNA (N/P ratio is 29) was increased with the post-transfection time (in 76 h), while the optimal transfection of Lipofectamine (TM) 2000/DNA was obtained at 24 h. The transfection of CSO-SA was not interfered in the presence of 10% fetal bovine serum, which showed remarkable enhancement effect. The optimal transfection efficiency of CSO-SA micelles in A549 cells was about 15%, which was higher than that of CSO (about 2%) and approach to that of Lipofectamine (TM) 2000 (about 20%). The low cytotoxic biodegradable CSO-SA micelles could be used as an effective DNA condensation carrier for gene delivery system. (c) 2006 Elsevier B.V. All rights reserved.