奥沙利铂白蛋白纳米粒的制备及其应用于结直肠癌腹腔化疗的研究  

Preparation and Experimental Application of Oxaliplatin-loaded Alumin Nanoparticles for Intraperitoneal Chemotherapy in Colorectal Cancer

作　　者：李金明[1] 钱江辉 吴庭玉[1] 张纪伟[1] 沙先谊[2] 

机构地区：[1]上海交通大学医学院附属新华医院结直肠外科,上海200092 [2]复旦大学药学院,上海201203

出　　处：《中国医药工业杂志》2017年第12期1751-1757,共7页Chinese Journal of Pharmaceuticals

基　　金：上海市教委上海高校选拔培养优秀青年教师科研专项基金(jdy10112);上海交通大学医工交叉研究基金项目(YG2011MS32)

摘　　要：目前用于结直肠癌腹腔化疗的药物剂型有待改进,故设计制备了奥沙利铂白蛋白纳米粒用于结直肠癌腹腔化疗,以期阻断结直肠癌腹腔转移、肝转移和血行转移,及产生淋巴导向化疗效果。采用去溶剂-交联法成功制备了直径(104.0±8.9)nm的奥沙利铂白蛋白纳米粒,载药量8.4%,包封率45.93%,缓释时间10 h左右。奥沙利铂白蛋白纳米粒(A组)与奥沙利铂原料药(B组)均对人大肠癌HT29细胞株具有良好的、相近的体外抑制效应。但在裸鼠结直肠癌腹腔转移动物模型的体内试验中,奥沙利铂白蛋白纳米粒表现出了优异的腹腔化疗效果,2组裸鼠在d28、d35和d42时的肿瘤体积有显著差异(P<0.05);奥沙利铂白蛋白纳米粒d28、d35和d42的相对抑瘤率分别为85.17%、74.55%和81.27%,提示用其进行结直肠癌腹腔化疗可能具有深远的潜力和前景。The pharmaceutical dosage forms for intraperitoneal chemotherapy in colorectal cancer remain to be improved, so we design to prepare oxaliplatin-loaded albumin nanoparticles for intraperitoneal chemotherapy, in order to block the abdominal cavity metastasis, liver metastasis and blood metastasis of colorectal cancer, with a lymphatic system targeting chemotherapy effect. The oxaliplatin-loaded albumin nanoparticles were prepared by desolvationchemical crosslinking method, which were spherical with an average diameter of （104.0±8.9） nm, drug loading of 8.4%, encapsulation efficiency of 45.93%, and sustained-release for about 10 h. Oxaliplatin-loaded albumin nanoparticles （group A） and oxaliplatin （group B） had good inhibitory effects in vitro on human colon carcinoma cell line HT29, and both were close. But, in the experiment of nude mice models intraperitoneally implanted of colorectal cancer, oxaliplatinloaded albumin nanoparticles exhibited more excellent intraperitoneal chemotherapy effects, with relative tumor volume inhibitory rates of 85.17%, 74.55% and 81.27% at day 28, 35 and 42 after transplantation of HT29 cells. The tumor volumes between the group A and group B had significant differences at day 28, 35 and 42 （P〈0.05）. It indicated that intraperitoneal chemotherapy with oxaliplatin albumin nanoparticles for colorectal cancer might have a profound potential and prospect.

关 键 词：奥沙利铂 白蛋白 纳米粒 结直肠癌 腹腔化疗 淋巴导向化疗 

分 类 号：R944.9[医药卫生—药剂学]