高级检索

    易翠翠, 马梦雅, 吴超慧, 王金凤, 张振中, 任雪玲. 一种基于聚乳酸-聚组氨酸的新型口服药物递送载体[J]. 功能高分子学报, 2020, 33(6): 589-597. doi: 10.14133/j.cnki.1008-9357.20200403001
    引用本文: 易翠翠, 马梦雅, 吴超慧, 王金凤, 张振中, 任雪玲. 一种基于聚乳酸-聚组氨酸的新型口服药物递送载体[J]. 功能高分子学报, 2020, 33(6): 589-597. doi: 10.14133/j.cnki.1008-9357.20200403001
    YI Cuicui, MA Mengya, WU Chaohui, WANG Jinfeng, ZHANG Zhenzhong, REN Xueling. A Novel Oral Drug Delivery Carrier Based on Polylactide-Polyhistidine[J]. Journal of Functional Polymers, 2020, 33(6): 589-597. doi: 10.14133/j.cnki.1008-9357.20200403001
    Citation: YI Cuicui, MA Mengya, WU Chaohui, WANG Jinfeng, ZHANG Zhenzhong, REN Xueling. A Novel Oral Drug Delivery Carrier Based on Polylactide-Polyhistidine[J]. Journal of Functional Polymers, 2020, 33(6): 589-597. doi: 10.14133/j.cnki.1008-9357.20200403001

    一种基于聚乳酸-聚组氨酸的新型口服药物递送载体

    A Novel Oral Drug Delivery Carrier Based on Polylactide-Polyhistidine

    • 摘要: 首先通过酸酐开环的方法合成聚组氨酸(PLH),再与聚乳酸(PLA)缩合形成两亲性聚合物(PLA-PLH)。利用傅里叶变换红外光谱、核磁共振氢谱以及动态光散射对PLA-PLH的结构和形态进行表征;接着以抗肿瘤药物2-甲氧基雌二醇(2-ME)作为模型药物,通过溶剂交换法制备PLA-PLH/2-ME纳米粒,考察其载药量与包封率,并在细胞水平考察PLA-PLH/2-ME对肿瘤细胞增殖和迁移的抑制作用;最后以荧光染料1,1'-二十八烷基-3,3,3',3'-四甲基吲哚并花青碘化物(DIR)为荧光标记物,考察PLA-PLH/DIR口服后体内的分布情况。结果表明:PLA-PLH被成功构建,平均粒径为(224.93±13.05)nm;当PLA-PLH与2-ME的质量比为1∶0.6时,载药量和包封率分别达到(27.86±0.19)%和(64.38±0.50)%。细胞实验显示:PLA-PLH可以显著增加结肠癌细胞CT26对PLA-PLH/2-ME的摄取;相比于2-ME处理组,PLA-PLH/2-ME处理组CT26细胞的细胞增殖抑制率和细胞迁移抑制率都显著增加。小鼠及其主要脏器的活体成像结果显示,PLA-PLH可以减缓DIR经口给药后在胃肠道的降解,增加其在肠道区域的聚集。

       

      Abstract: Polyhistidine (PLH) was synthesized by ring-opening polymerization of anhydride, and then condensed with polylactide (PLA) to form an amphiphilic block copolymer (PLA-PLH). Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance hydrogen spectroscopy (1H-NMR) and dynamic light scattering (DLS) were used to characterize the structure and morphology of PLA-PLH nanoparticles. Using the anti-tumor drug 2-methoxyestradiol (2-ME) as a model drug, the drug delivery system PLA-PLH/2-ME was prepared by the solvent exchange method, and the drug loading and encapsulation efficiency were detected. At the cellular level, the inhibitory effects of the PLA-PLH/2-ME drug delivery system on CT26 colon cancer cells proliferation and migration were investigated. Finally, a fluorescent dye 1,1'-octacosyl-3,3,3',3'-tetramethylindocyanine iodide (DIR) was used as the fluorescent marker, and the distribution of PLA-PLH/DIR in vivo was investigated. Results showed that PLA-PLH nanoparticles were successfully constructed, with an average particle diameter of (224.93±13.05) nm. When the mass ratio of PLA-PLH to 2-ME was 1∶0.6, the drug loading and encapsulation efficiency were (27.86±0.19)% and (64.38±0.50)%, respectively. In cellular experiments, PLA-PLH could significantly enhance the uptake of the drug system by CT26 cells. Compared with free 2-ME treated group, the cell proliferation inhibition rate and cell migration inhibition rate of CT26 cells treated with PLA-PLH/2-ME group were increased significantly. In vivo imaging of mice and ex vivo imaging of various major tissues studies showed that PLA-PLH nanoparticles could reduce the degradation of DIR in the gastrointestinal tract and enhance the accumulation of DIR in colon region after oral administration.

       

    /

    返回文章
    返回