紫杉醇自组装核壳型纳米胶束的制备与性能  

Preparation and properties of self-assemble paclitaxel-loaded core-shell type nano-micelles

作　　者：余巧[1] 潘仕荣[1] 杜卓[1] 

机构地区：[1]中山大学药学院,广东广州510080

出　　处：《药学学报》2008年第4期408-414,共7页Acta Pharmaceutica Sinica

摘　　要：本文合成了聚乙二醇-聚谷氨酸苄酯（polyethylene glycol-polybenzyl-L-glutamate，PEG-PBLG）两亲嵌段共聚物，并采用超微透析法制备了紫杉醇／PEG-PBLG核壳型纳米胶束。通过高效液相色谱测定了胶束的载药量及药物包封率；采用动态光散射法测定了胶束的粒径及分布；通过体外试验研究了紫杉醇／PEG-PBLG胶束的释药特性；采用四噻唑蓝法考察了紫杉醇／PEG-PBLG胶束的体外细胞毒性；通过裸鼠的抑瘤试验评价了紫杉醇胶束对人肝癌细胞的疗效。结果表明，PEG-PBLG胶束能包埋疏水性药物紫杉醇；紫杉醇／PEG-PBLG胶束的粒径为80—265nm，且随着载体共聚物PBLG嵌段相对分子质量的升高而增大；紫杉醇／PEG-PBLG胶束的体外释放具有缓释特性；当紫杉醇浓度大于20μg·mL^-1时，紫杉醇／PEG-PBLG胶束的细胞毒性低于相应浓度的紫杉醇／聚氧乙烯蓖麻油注射剂（P〈0．05），紫杉醇／PEG-PBLG胶束具有与紫杉醇／聚氧乙烯蓖麻油注射剂相似的抑制肿瘤作用。综上所述，紫杉醇／PEG-PBLG纳米胶束具有较均匀的粒径及粒径分布、缓释特性、低毒和较好的抗肿瘤作用。Polyethylene glycol-polybenzyl-L-glutamate copolymer （PEG-PBLG） was synthesized and paclitaxel-loaded core-shell type nano-micelles with amphiphilic copolymer PEG-PBLG was prepared by the dialysis method. The drug loading content and entrapment efficiency were determined by HPLC. The average size and its distribution were determined by dynamic light scattering method. The paclitaxel release rate in vitro from micelles was measured by HPLC. The cell cytotoxicity in vitro was observed with MTT assay. The anti-tumor activity of paclitaxel-loaded micelles were evaluated in tumor-inhibiting test of nude mice using human liver cancer HepG-2. The results indicated that paclitaxel could be entrapped in PEG-PBLG copolymer micelles and its size was in the range of 80 - 265 nm which increased with an increase in molecular weight of PBLG in copolymer; in vitro the paclitaxel could be released sustainably from the micelles. In high concentration of paclitaxel （ 〉 20 μg · mL^- 1 ） the paclitaxel-loaded PEG-PBLG micelles displayed much less cell cytotoxicity than paclitaxel injections with Cremophor EL （ P 〈 0. 05 ） ; the tumor inhibiting activity of paclitaxel-loaded PEG-PBLG micelles was similar to that of paclitaxel injections with Cremophor EL in the same paclitaxel concentration. It was concluded that the paclitaxel- loaded PEG-PBLG micelles had more uniform size and size distribution, excellent drug sustainable-release behavior, less cytotoxicity, good anti-tumor activity similar to paclitaxel injections with Cremophor EL. So paclitaxel-loaded PEG-PBLG micelles would be a novel paclitaxel preparation in clinic for the treatment of tumor.

关 键 词：紫杉醇 聚乙二醇-聚谷氨酸苄酯嵌段共聚物 纳米胶束 细胞毒性 抑瘤试验 

分 类 号：R934.4[医药卫生—生药学]