载紫杉醇重组高密度脂蛋白微球的制备和抗胃癌作用研究  

Preparation of paclitaxel loaded recombinant high density lipoprotein microspheres and its anti-gastric cancer effect

作　　者：王青 杨觅[2] WANG Qing;YANG Mi(Department of Geriatrics,Nanjing DrumTowel Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing 210000,China)

机构地区：[1]南京大学医学院附属鼓楼医院老年科,210000 [2]南京大学医学院附属鼓楼医院肿瘤科,210000

出　　处：《浙江医学》2020年第2期118-122,126,I0003,共7页Zhejiang Medical Journal

基　　金：国家自然科学基金面上项目（81271741）

摘　　要：目的载紫杉醇重组高密度脂蛋白(PTX-rHDL)微球体内外抗胃癌的观察效果。方法采用超声重组法,利用无毒溶剂制备PTX-rHDL微球并作用于人胃癌细胞和小鼠胃癌模型,观察其形态、稳定性、包封率、载药率,以及对胃癌细胞的毒性和小鼠胃癌模型的抗肿瘤作用。结果制得的PTX-rHDL微球外观良好、稳定性强,粒径(60.41±1.81)nm,包封率为(95.59±0.09)%,载药率为(3.86±0.90)%,体外释放试验显示其具有良好的缓释特性。在细胞摄取实验中,rHDL微球被高度表达SR-B1的人胃癌细胞株MGC-7901摄取,MTT结果显示PTX-rHDL微球对人胃癌细胞株MGC-7901的细胞毒性强于人胃癌细胞株MKN-45。体内实验中,PTX-rHDL微球的抗肿瘤作用及耐受性均优于PTX裸药。结论本研究制备的PTX-rHDL微球性质稳定,具有缓释作用,可以提高体内外抗肿瘤疗效。Objective To prepare paclitaxel loaded recombinant high density lipoprotein microspheres(PTX-rHDL)and to investigate its anti-gastric effect in vivo and in vitro.Methods PTX-rHDL nanoparticles were formulated without adding any toxic organic solvents,surfactants or other toxic agents by ultrasound recombination method.The stability,morphology,encapsulation efficiency,drug-loading capacity of the prepared PTX-rHDL were characterized.Its anti-gastric cancer effects were tested in cultured human gastric cancer cell lines SGC-7901 and MKN-45 and Balb/c nude mice bearing human gastric cancer SGC-7901.Results The size of PTX-rHDL was(60.41±1.81)nm.The encapsulation efficiency reaching(95.59±0.09)%with the drug loading content of(3.86±0.90)%.In vitro release study indicated the controlled release pattern of PTX-rHDL nanoparticles.In cellular uptake experiments,NBD-PE containing rHDL nanoparticles were uptake by human gastric cancer MGC-7901 cells highly expressing SR-B1.The cytotoxicity of PTX-rHDL nanoparticles to MGC-7901 cells was higher than that to MKN-45 cells.Studies with tumor-bearing mice showed that PTX-rHDL nanoparticles were substantially better tolerated and had better antitumor effect than PTX alone.Conclusion The prepared drug-loaded-nano system is stable and can release sustainably,indicating a promising prospect in clinic use.

关 键 词：紫杉醇 药物传输 高密度脂蛋白 微球 胃癌 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]