载药肿瘤微血管栓塞颗粒制备及其抗肿瘤作用初探

Preparation of drug-loaded nanoparticles used for tumor microvascular embolization and its antitumor effect:a preliminary study in vitro

目的制备加载化疗药物的纳米微粒,研究其性质及体外释药特点,探讨体外对人原代肝癌细胞的毒性作用,为用于临床肿瘤微血管介入栓塞提供理论依据。方法以盐酸吉西他滨-复方甘草酸苷共聚物为药物载体,加载化疗药物多柔比星制备载药纳米微粒。扫描电镜观察微粒形态,纳米粒度电位仪检测微粒粒径分布及电位,高效液相色谱法计算载药率及包封率,透析袋扩散法作体外释放动力学试验,体外考察纳米药物稳定性及释药性能。CCK-8法检测纳米药物在体外对人原代肝癌细胞的毒性作用。结果本法制备的载药纳米微粒外观呈圆球形,平均粒径(62.83±5.19)nm,平均电位-17.9 mV;载药率、包封率分别为3.16%、66.27%;有良好的缓释特性,对人原代肝癌细胞生长有明显抑制作用。结论本法制备的载药纳米微粒具有较好的药物缓释性及抗肿瘤效应,是一种具有良好应用前景的抗肿瘤纳米药物。

Objective To prepare a new type of drug-loaded nanoparticles, to study its properties and drug-release characteristics in vitro, to investigate its antitumor effect on human primary hepatocellular carcinoma ceils, and to provide theoretical basis for clinical tumor microvascular interventional embolization therapy. Methods Gemcitabine hydrochloride and compound glycyrrhizin were mixed and used as the drug carrier, and chemotherapeutic drug, doxorubiein, was added for the preparation of drug-loaded nanoparticles. The surface structure and morphology of the drug-loaded nanoparticles were examined by scanning electron microscopy; the particle size distribution and the potential of the nanoparticles were analyzed by Zata potential and nano-particle size analyzer; the drug-loaded rate and encapsulation rate were measured by high performance liquid chromatography （HPLC） ; the in vitro drug-release kinetics experiment was conducted with dialysis bag diffusion method; the stability and drug-release properties of nano-drug were investigated in vitro. The toxic effect of nano-drug on human primary hepatocellular carcinoma cells in vitro was determined by CCK-8 assay. Results The drug-loaded nanoparticles prepared by this method had a mean size of （62.83±5.19） nm with a spherical appearance, and its average potential was -17.9 inV. The drug-loaded rate and encapsulation rate were 3.16% and 66.27% respectively. The drug-loaded nanoparticles possessed excellent sustained release characteristics and showed obvious inhibitory effect on human primary hepatocellular carcinoma cells.Conclusion The drug-loaded nanoparticles prepared by this method have excellent sustained release characteristics and antitumor effect, therefore, this nano-drug is an anti-tumor medicine with good clinical application prospects.