摘要
目的制备壳聚糖修饰的脂质体,考察不同相对分子质量壳聚糖对脂质体性质的影响。方法本实验将壳聚糖通过静电作用修饰到脂质体表面,制备了3种不同相对分子质量壳聚糖修饰的脂质体(chitosan-modified liposomes;CMLs),用透射电镜、激光衍射粒度分析仪测定CMLs的形态、粒径和表面电位;通过葡聚糖凝胶柱分离脂质体和游离的壳聚糖,计算壳聚糖的结合率;并且对CMLs在体外血清条件下的稳定性以及细胞毒性进行了考察。结果制备得到CMLs粒度均匀,Zeta电位均在+40mV左右;不同相对分子质量壳聚糖在脂质体上的结合率分别为44.13%,88.50%,84.40%。血清存在条件下,相比于空白脂质体,较高相对分子质量CMLs具有更好的稳定性和抗血清能力。CMLs的细胞毒性要小于阳离子脂质体。结论CMLs具有作为基因给药载体的优点,特别是在体内应用中将会有很好的前景。
Abstract
OBJECTIVE To prepare chitosan-modified liposomes and investigate the influence on liposomes caused by different molecular weight chitosan. METHODS Three different chitosan-modified liposomes (CMLs) were prepared. The properties of CMLs,such as the morphology,average size and Zeta potential,were detected. Sephadex column was used to isolate liposomes and free chitosan. The stability of CMLs in serum condition (10%) was studied,as well as the cytotoxicity of CMLs using MTT assay. RESULTS All CMLs were spherical and Zeta potential was about +40 mV. The rates of chitosan modification were 44.13%,88.50%,84.40%,respectively. Compared to unmodified liposomes,the liposomes modified with higher molecular weight chitosan possessed better stability in serum condition. CMLs showed lower cytotoxicity than cationic liposomes in vitro. CONCLUSION CMLs can be a promising gene delivery vector,especially for in vivo application.
关键词
脂质体 /
壳聚糖 /
稳定性 /
细胞毒性
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Key words
liposomes /
chitosan /
stability /
cytotoxicity
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帅武平;张幸国;陈金亮;何彩丽;梁文权;高建青.
壳聚糖修饰脂质体的制备和性质研究[J]. 中国药学杂志, 2007, 42(15): 1159-1163
SHUI Wu-ping;ZHNG Xing-guo;CHEN Jin-ling;HE Ci-li;LING Wen-qun;GO Jin-qing.
Preparation and Characterization of Chitosan-Modified Liposomes [J]. Chinese Pharmaceutical Journal, 2007, 42(15): 1159-1163
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脚注
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基金
国家自然科学基金资助项目(30572270);浙江省科技重点攻关项目(2006C23015);浙江省医药卫生科技计划(2007B063)
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