载紫杉醇纳米诊疗体的制备及初步应用

发布时间：2018-03-13 08:32

本文选题：紫杉醇　切入点：纳米诊疗体　出处：《上海交通大学学报(医学版)》2017年02期 　论文类型：期刊论文

【摘要】：目的·以生物可降解聚乳酸乙醇酸-甲氧基聚乙二醇(PLGA-m PEG)为骨架,构建包载紫杉醇(PTX)的有机高分子超声纳米诊疗体,初步验证其在胰腺癌体表种植瘤的超声造影显像效果及体外抗肿瘤作用。方法·采用复乳法制备载PTX的PLGA-m PEG超声纳米诊疗体(PTX-NPs),并通过设计四因素三水平的正交试验,以包封率和载药量为考查指标,对制备条件进行优化,得出最佳工艺参数。超细微粒粒度/电位分析仪检测所构建的PTX-NPs平均粒径和电位,透射电子显微镜(TEM)检测纳米诊疗体大小、形态、分布、团聚等情况。检测PTX-NPs在体外和裸鼠胰腺癌体表种植瘤的超声造影显像。CCK-8试验检测PTX-NPs的体外抗肿瘤效果。结果·成功制备PTX-NPs,包封率和载药率分别为(91.32±3.25)%和(2.666±0.092)%。超声纳米诊疗体的平均粒径为(80.6±3.8)nm,电位为(-13.4±1.5)mv;TEM证实PTX-NPs呈球形、表面光滑、分布均匀、无明显团聚现象。PTX-NPs在体外和胰腺癌体表种植瘤的超声造影显像良好。CCK-8试验结果显示,该纳米诊疗体能显著降低细胞生存率,且同时给予超声照射(US)或超声靶向破坏微泡(UTMD)可进一步降低细胞生存率。结论·PTX-NPs在胰腺癌体表种植瘤的超声造影显像效果良好;在离体状态下,PTX-NPs具有一定的抗肿瘤治疗效果,且US和UTMD能增强该纳米诊疗体的离体抗肿瘤作用。
[Abstract]:Objective: to construct an organic polymer ultrasonic nanotherapeutics containing paclitaxel (PTX) by using biodegradable polylactic glycolic acid-methoxy polyethylene glycol (PLGA-m PEG) as the skeleton. To preliminarily verify the effect of contrast-enhanced imaging and in vitro anti-tumor effect of implanted tumor of pancreatic cancer. Methods: the PTX loaded PLGA-m PEG ultrasonic nanotherapeutic body was prepared by using the method of multiple milk, and four factors and three levels of orthogonal experiment were designed. Taking encapsulation efficiency and drug loading as test indexes, the preparation conditions were optimized and the optimum process parameters were obtained. The average particle size and potential of PTX-NPs were measured by ultrafine particle size / potential analyzer. Transmission electron microscopy (TEM) was used to detect the size, morphology and distribution of nanosurgery. In vitro, CCK-8 test was used to detect the antitumor effect of PTX-NPs. Results: the encapsulation rate and drug loading rate of PTX-NPs were 91.32 卤3.25% and 2.666 卤0.092% respectively. The mean diameter of the diagnosis and treatment body was 80.6 卤3.8nmand the potential was -13.4 卤1.5mvTem. The PTX-NPs was spherical. The surface was smooth, the distribution was uniform, and there was no obvious agglomeration. The ultrasound imaging of implanted tumor in vitro and on the body surface of pancreatic cancer was good. The results of CCK-8 test showed that the nano-diagnosis and treatment could significantly reduce the cell survival rate. The survival rate of pancreatic cancer cells was further reduced by ultrasound irradiation (USS) or ultrasound targeted destruction of microbubbles (UTMD). Conclusion: PTX-NPs has a good effect on imaging of pancreatic carcinoma, and PTX-NPs has a certain antitumor effect in vitro. Us and UTMD can enhance the in vitro anti-tumor effect of the nano-therapy.
【作者单位】：上海交通大学附属第一人民医院松江分院超声科;上海交通大学附属第一人民医院超声科;上海交通大学医学院附属仁济医院肿瘤研究所国家肿瘤及基因研究重点实验室;
【基金】：国家自然科学基金(81271596,81171352,81501483)~~
【分类号】：R943

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