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The use of non-viral delivery systems has numerous advantages in the area of gene therapy as this approach could circumvent the safety issues that may occur when using viral vectors. Hydrophobically modified chitosan containing five deoxycholic acid groups per 100 anhydroglucose units was synthesized to prepare self-aggregated nanoparticles in aqueous media and utilized to form complexes with plasmid DNA. Formation and various characteristics of DNA/chitosan self-aggregate complexes were investigated by electrophoresis, zeta potential measurement, and dynamic light scattering method. It was hypothesized that complex formation between DNA and chitosan self-aggregates can be strongly dependent on the charge ratio, pH, and incubation time. Migration of DNA on an agarose gel was completely retarded over a charge ratio (+/−) of 4/1 at pH 7.2, and the mean diameter of the complexes was determined to be 350 nm with unimodal size distribution (+/−=4/1; pH 7.2; incubation time, 30 min). The complex formation behavior was also regulated by pH of the media. The incubation time was unlikely to be the critical factor affecting the complex formation behavior due to the instant electrostatic interactions between negatively charged DNA and positively charged chitosan self-aggregates. This approach to controlling the characteristics of DNA/self-aggregate complexes could be critical in the design and tailoring of novel gene delivery systems using non-viral vectors. 相似文献
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壳聚糖-脱氧胆酸及其叶酸偶联体的表征及自组装特性研究 总被引:4,自引:0,他引:4
以1-乙基-(3-二甲基氨基丙基)碳酰二亚胺(EDC)为催化剂,将脱氧胆酸接枝到壳聚糖主链的氨基上,得到疏水改性的双亲性壳聚糖;再将叶酸连接于壳聚糖氨基,可得到具有肿瘤靶向潜力的双亲性共聚物.利用红外光谱、1H核磁、X射线晶体衍射图谱对其结构进行表征.脱氧胆酸-壳聚糖、叶酸-壳聚糖-脱氧胆酸在水相中通过透析处理均能形成自聚集体,利用荧光探针技术研究其自聚集行为.制得的两种自聚集体均具有较低的临界胶束浓度(10-2mg/ml),透射电镜和粒径分析测试显示制得的自聚集体为纳米级颗粒.随着脱氧胆酸取代度的增加,粒径降低,临界胶束浓度下降,但叶酸直接偶联壳聚糖导致自组装阻力增加. 相似文献
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