Wang Ya-Jie, Wang Jie, Hao Dan-Li, Yue Qiao-Xin, Xie Ran, DE Ge-Jing, Yi Hong, Zang Chen, Zhao Qing-He, Chen Yan-Jun
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2019 Jun;44(11):2251-2259. doi: 10.19540/j.cnki.cjcmm.20190326.305.
Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-β-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.
本研究制备了载多西他赛的纳米胶束，以提高多西他赛（DTX）的溶解度和肿瘤靶向作用，并进一步评估其体外抗癌效果。采用薄膜水化法制备PBAE-DTX纳米胶束，分别用两亲性嵌段共聚物聚乙二醇甲氧基-聚丙交酯（PELA）和pH敏感三嵌段共聚物聚乙二醇甲氧基-聚丙交酯-聚-β-氨基酯（PBAE）制备PELA-DTX纳米胶束和PBAE-DTX纳米胶束。对纳米胶束进行理化性质表征，并研究其对小鼠Lewis肺癌细胞的活性。粒径测定结果表明，空白胶束和载药胶束粒径相似，范围为10至100nm。PBAE胶束在弱酸性条件下粒径发生变化，具有良好的pH响应性。通过高效液相色谱法测定上述两种载DTX纳米胶束的包封率分别为（93.8±1.70）%和（87.2±4.10）%，载药量分别为（5.3±0.10）%和（4.9±0.05）%。此外，通过MTT法检测发现DTX胶束对Lewis肺癌细胞也有显著抑制作用，且pH敏感的PBAE-DTX表现出更好的细胞毒性。流式细胞术结果表明，DTX组、PELA-DTX组和PBAE-DTX组在处理48h后，肺癌Lewis细胞的凋亡率分别为（20.72±1.47）%、（29.71±2.38）%和（40.91±1.90）%（P<0.05）。结果表明，不同的多西他赛制剂均可促进Lewis细胞凋亡，且PBAE-DTX具有更强的促凋亡作用。负载pH敏感型DTX的胶束有望成为在酸性肿瘤微环境中开发刺激触发药物递送系统的候选药物，可提高对Lewis肺癌肿瘤生长的抑制作用。
