川芎嗪壳聚糖纳米粒的制备及体外靶向分布研究

Preparation and in vitro targeted delivery of chitosan nanoparticles loaded with ligustrazine

目的:制备川芎嗪壳聚糖纳米粒,考察纳米粒在人癌细胞的靶向分布。方法:以壳聚糖为载体,用离子交联法制备川芎嗪纳米粒。用激光粒度分析仪检测粒径,用透射电镜观察纳米粒的形态。用HPLC法测定纳米粒的包封率、载药量和体外释放度。以川芎嗪溶液为对照,测定纳米粒在人乳腺癌MCF-7细胞株、人肺腺癌A549细胞株和人白血病K562细胞株中的浓度,评价其靶向性。结果:制备的川芎嗪壳聚糖纳米粒为圆球形,平均粒径为(118.6±2.2)nm,分散系数(0.117±0.016)(n=3),包封率(79.7±0.4)%,载药量(24.3±0.2)%,缓慢释药96h累积释药率达75%。纳米粒在人乳腺癌MCF-7细胞株、人肺腺癌A549细胞株和人白血病K562细胞株中的浓度显著高于川芎嗪溶液(P<0.05)。结论:制备的川芎嗪壳聚糖纳米粒对人癌细胞有靶向浓集作用。

Objective：To prepare chitosan nanopartieles loaded with ligustrazine and investigate their targeted delivery in human cancer cells. Methods..Chitosan nanoparticles loaded with ligustrazine were prepared by using ionic gelation method. The particle diameter was determined by laser partical size analyzer and morphology of the nanopartieles was detected by transmission electron microscope. The encapsulation efficiency,loading capacity and in vitro release rate of the nanoparticles were determined by HPLC method. The intraceliular concentrations of the nanoparticles in human breast cancer MCF-7 ceil lines, human adenocarcinoma of lung A549 cell lines and human leukemia K562 cell lines were determined and targeted characteristics of the nanoparticles were evaluated using ligustrazine solution as control. Results The chitosan nanoparticles were spherical with an average diameter （ 118.6 ± 2.2） nm and polydispersion index （0.11 7 ± 0.016） （n = 3 ）. The encapsulation efficiency and loading capacity were （79.7 ± 0.4） % and （24.3 ± 0.2） %, respectively. The in vitro cumulative slow release rate was about 75% in 96 h. The intracellular concentrations of nanoparticles in human cancer cells were significantly higher than that of ligustrazine solution （P〈0.05）. Conclusion： The prepared chitosan nanoparticles loaded with ligustrazine are featured with tumor-targeting drug delivery characteristics.