Zhang Ting, Zhou Songlei, Liu Yang, Luo Xiang, Di Donghua, Song Yanzhi, Liu Xinrong, Deng Yihui
a College of Pharmacy , Shenyang Pharmaceutical University , Shenyang , P.R. China.
Drug Dev Ind Pharm. 2017 Nov;43(11):1827-1835. doi: 10.1080/03639045.2017.1349784. Epub 2017 Jul 26.
In our previous study, polysialic acid-octadecyl dimethyl betaine (PSA-BS18) was synthesized and modified to liposomal EPI. Preliminary experiments revealed that the PSA-BS18 was a potential material for targeting tumor site with superior curative effects. In this study, PSA-BS18 and Pluronic F127 (F127) mixed polymeric micelles encapsulated docetaxel (DTX) (FP/DTX) were prepared by a self-assembly method. The FP/DTX was found to have a diameter of 34.83 ± 0.50 nm with a narrow polydispersity, the entrapment efficiency was 99.12 ± 1.17%, and the drug loading efficiency of 1.40 ± 0.01%. The storage and dilution stability of FP/DTX was fine. In vitro release studies demonstrated that FP/DTX had delayed the drug release from the micelles. In vitro cytotoxicity assay on B16 cells presented that FP/DTX led to a stronger cytotoxic activity in comparison to F127 micelles based DTX (F127/DTX) and Tween80-based DTX (Taxotere). The in vivo imaging study showed that the accumulation of FP/DTX at tumor sites was more than F127/DTX. The in vivo antitumor activity of FP/DTX against B16 tumor xenograft model showed a significant higher inhibition and a lower toxicity compared with F127/DTX and Taxotere. Taken together, the results obtained above showed that PSA-BS18 and F127 mixed polymeric micelles may be a promising strategy for antitumor delivery of DTX.
在我们之前的研究中，合成了聚唾液酸-十八烷基二甲基甜菜碱（PSA-BS18）并将其修饰到脂质体表柔比星上。初步实验表明，PSA-BS18是一种具有潜在靶向肿瘤部位且疗效优异的材料。在本研究中，通过自组装方法制备了PSA-BS18与普朗尼克F127（F127）混合的聚合物胶束包裹多西他赛（DTX）（FP/DTX）。发现FP/DTX的直径为34.83±0.50纳米，多分散性窄，包封率为99.12±1.17%，载药效率为1.40±0.01%。FP/DTX的储存和稀释稳定性良好。体外释放研究表明，FP/DTX延缓了药物从胶束中的释放。对B16细胞的体外细胞毒性试验表明，与基于F127胶束的DTX（F127/DTX）和基于吐温80的DTX（泰索帝）相比，FP/DTX具有更强的细胞毒性活性。体内成像研究表明，FP/DTX在肿瘤部位的蓄积比F127/DTX更多。FP/DTX对B16肿瘤异种移植模型的体内抗肿瘤活性显示，与F127/DTX和泰索帝相比，具有显著更高的抑制作用和更低的毒性。综上所述，上述结果表明PSA-BS18和F127混合聚合物胶束可能是一种有前景的多西他赛抗肿瘤递送策略。
