摘要
以新型高分子材料N-glycyrrhetinic acid(GA)-polyethylene glycol(PEG)-chitosan(NGPC)为载体材料,采用离子交联法制备载马钱子碱(Brucine)的壳聚糖纳米粒(Brucine/NGPC-NPs)。以Hep G2细胞为模型细胞,考察药物作用时间、药物作用浓度、加入外源甘草次酸和细胞内吞抑制剂对细胞摄取的影响,并结合激光共聚焦显微镜成像技术观察纳米粒在细胞内的转运。结果显示,Brucine/NGPC-NPs平均粒径为(197.6±11.2)nm,包封率和载药量分别为(63.48±4.67)%和(5.49±0.38)%。Hep G2细胞对马钱子碱溶液剂和Brucine/NGPC-NPs的摄取均具有时间和浓度依赖性,其中对NGPC-NPs的摄取明显强于溶液剂,具有显著的主动转运特征,且摄取量随外源甘草次酸的加入而减少,其摄取途径主要依赖网格蛋白介导的内吞,之后被细胞内化。结果表明,NGPC-NPs可以作为肝细胞靶向的载体,显著提高药物进入肝癌细胞的量,达到减毒增效的目的。
A novel polymer material N-glycyrrhetinic acid（ GA）-polyethylene glycol（ PEG）-chitosan（ NGPC）was used as a targeting carrier of Brucine,and then the Brucine-loaded NGPC-NPs（ Brucine / NGPC-NPs） were prepared by ionic crosslinking method. The effect of the action of brucine, the brucine concentration, GA and endocytic inhibitors on the cell uptakes of Brucine solution and Brucine / NGPC-NPs were investigated in human Hep G2 hepatocellular carcinoma cells. The confocal laser scanning microscopy was used to observe qualitatively the nanoparticles internalization. The results showed that the mean size of Brucine / NGPC-NPs were（ 197. 6 ±11. 2） nm; the drug encapsulation efficiency and loading content was（ 63. 48 ± 4. 67） % and（ 5. 49 ± 0. 38） %,respectively. The cellular uptake of Brucine solution and Brucine / NGPC-NPs were time-and concentration dependent. In particular,the Brucine / NGPC-NPs could be more efficiently taken up by cells than Brucine solution,with a significant active transport characteristics. Moreover, the presence of free glycyrrhetinic acid could decrease the cell uptake of Brucine / NGPC-NPs,indicating that the uptake of nanoparticles might mainly rely on clathrin-mediated endocytosis,and then internalized by cells. Hence,NGPC-NPs could be a targeting carrier to facilitate the delivery of encapsulated Brucine into the human hepatic cancer cells,achieving the goal of reducing poison and increasing effects.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2014年第6期674-680,共7页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.81102814)
江苏省高等学校大学生创新创业训练计划资助项目(No.201310315035Z)
江苏省中药资源产业化过程协同创新中心资助项目~~
