95%。PTX-OA/BJO CMNEs對HepG-2細(xì)胞的毒性作用有濃度和時(shí)間依賴性，細(xì)胞周期試驗(yàn)表明PTX-OA/BJO CMNEs增加了G2/M期阻滯。注射PTX-OA/BJO CMNEs后的裸鼠模型中，對比注射生理鹽水組，裸鼠腫瘤體積明顯減少 (P<0.05)，表明PTX-OA/BJO CMNEs在體內(nèi)有很好抗腫瘤效果。進(jìn)一步研究發(fā)現(xiàn)，PTX-OA/BJO CMNEs的抗腫瘤作用增強(qiáng)與誘導(dǎo)腫瘤細(xì)胞凋亡的能力有關(guān)，尤其是PTX-OA/BJO CMNEs可明顯抑制腫瘤細(xì)胞的增殖和TOPO II的活性。結(jié)論 不同機(jī)制的兩種藥物聯(lián)合給藥能同時(shí)阻斷不同的抗癌途徑，從而提高治療反應(yīng)，降低毒性。;Objective Developed the core-matched nanoemulsions (CMNEs) to co-delivery paclitaxel-oleic acid prodrug (PTX-OA) and brucea javanica oil (BJO) for increasing the antitumor effect.. Methods Antitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy which based on core-matched technology (CMT) were evaluated in vitro and in vivo. Results The PTX-OA/BJO CMNEs were of nanoscale particle size (108.7 ± 2.3) nm and with entrapment efficiency of > 95%. The PTX-OA/BJO CMNEs displayed concentration and time-dependent cytotoxicity against HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of the tumor volume with no obvious toxicity was observed in nude mice model following administration of PTX-OA/BJO CMNEs compared with the control treated with normal saline (P < 0.05), which suggested the excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEs were associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibiting tumor cell proliferation and the activity of TOPO Ⅱ. Conclusion Co-encapsulation of two drugs with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity."/>

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Archive > Volume 10 Issue 3 > 2018,10(3):310-317 Prev Next

紫杉醇和鴉膽子油分子配型納米乳的制備及抗腫瘤作用的體內(nèi)外評價(jià)

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Preparation and evaluation of Paclitaxel and Brucea Javanica oil core-matched nanoemulsions to treat cancer in vitro and in vivo

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    摘要:
    目的 制備共同時(shí)遞送紫杉醇-油酸前藥(PTX-OA)和鴉膽子油(BJO)的分子配型納米乳制劑(CMNEs)。方法 對基于分子配型組裝技術(shù)的紫杉醇-油酸/鴉膽子油納米乳制劑體外對HepG2細(xì)胞的抑制、細(xì)胞周期、細(xì)胞凋亡和體內(nèi)抑制裸鼠腫瘤生長的評價(jià)。結(jié)果 紫杉醇-油酸/鴉膽子油納米乳（PTX-OA/BJO CMNEs）粒徑為108.7 2.3 nm，包封率> 95%。PTX-OA/BJO CMNEs對HepG-2細(xì)胞的毒性作用有濃度和時(shí)間依賴性，細(xì)胞周期試驗(yàn)表明PTX-OA/BJO CMNEs增加了G2/M期阻滯。注射PTX-OA/BJO CMNEs后的裸鼠模型中，對比注射生理鹽水組，裸鼠腫瘤體積明顯減少 (P<0.05)，表明PTX-OA/BJO CMNEs在體內(nèi)有很好抗腫瘤效果。進(jìn)一步研究發(fā)現(xiàn)，PTX-OA/BJO CMNEs的抗腫瘤作用增強(qiáng)與誘導(dǎo)腫瘤細(xì)胞凋亡的能力有關(guān)，尤其是PTX-OA/BJO CMNEs可明顯抑制腫瘤細(xì)胞的增殖和TOPO II的活性。結(jié)論 不同機(jī)制的兩種藥物聯(lián)合給藥能同時(shí)阻斷不同的抗癌途徑，從而提高治療反應(yīng)，降低毒性。

    Abstract:
    Objective Developed the core-matched nanoemulsions (CMNEs) to co-delivery paclitaxel-oleic acid prodrug (PTX-OA) and brucea javanica oil (BJO) for increasing the antitumor effect.. Methods Antitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy which based on core-matched technology (CMT) were evaluated in vitro and in vivo. Results The PTX-OA/BJO CMNEs were of nanoscale particle size (108.7 ± 2.3) nm and with entrapment efficiency of > 95%. The PTX-OA/BJO CMNEs displayed concentration and time-dependent cytotoxicity against HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of the tumor volume with no obvious toxicity was observed in nude mice model following administration of PTX-OA/BJO CMNEs compared with the control treated with normal saline (P < 0.05), which suggested the excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEs were associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibiting tumor cell proliferation and the activity of TOPO Ⅱ. Conclusion Co-encapsulation of two drugs with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity.

    關(guān)鍵詞:
    紫杉醇;鴉膽子油;分子配型納米乳;癌癥;聯(lián)合治療

    Keywords:


    Project Supported:
    National Nature Science Foundation of China (81403109) and Science and Technology Planning Project of Guangdong Province (2014A020210021, 2016A020217017)

    Clc Number:

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