【摘要】 为提高多西紫杉醇(DTX)的水溶性及靶向性,降低不良反应,采用pH敏感聚乙二醇单甲醚-聚乳酸-聚-β-氨基酯(polyethyleneglycol methoxy-polylactide-poly-β-aminoester,PBAE)和非pH敏感聚乙二醇单甲醚-聚乳酸(polyethyleneglycol methoxy-polylactide,PELA)2种聚合物材料,分别包载多西紫杉醇制成纳米胶束(PBAE-DTX,PELA-DTX),对胶束进行理化性质表征并研究其对小鼠Lewis肺癌细胞的活性作用。粒度测定结果显示空白及载药胶束粒径相近,均在10～100 nm;PBAE胶束在弱酸性条件下粒径发生变化,pH响应性较好;制备的2种载药胶束中DTX的包封率分别为(93.8±1.70)%,(87.2±4.10)%,载药量分别为(5.3±0.10)%,(4.9±0.05)%;MTT检测载药胶束对Lewis肺癌细胞的增殖均有明显的抑制作用,pH敏感的PBAE-DTX表现出更好的细胞毒性活性;流式细胞仪检测结果显示,给药48 h后DTX,PELA-DTX,PBAE-DTX 3组的凋亡细胞率分别为(20.72±1.47)%,(29.71±2.38)%,(40.91±1.90)%(P<0.05),表明不同多西紫杉醇制剂均能促进Lewis细胞的凋亡,PBAE-DTX的促凋亡作用更强。pH敏感性的PBAE-DTX载药胶束制备简单,稳定性好,能显著抑制Lewis肺癌细胞增殖并诱导细胞凋亡。更多还原

【Abstract】 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.更多还原