载5-氟尿嘧啶两亲多糖纳米粒的制备及其对肝癌细胞HepG2的杀伤作用  

Preparation of 5-Fluorouracil Encapsulated in Amphiphilic Polysaccharide Nano-micelles and Its Killing Effect on Hepatocarcinoma Cell Line HepG2

作　　者：周嘉嘉[1] 陈汝福[1] 唐启彬[1] 周泉波[1] 卢红伟[2] 王捷[1] 

机构地区：[1]中山大学附属第二医院肝胆外科,广东广州510120 [2]中山大学化学与化学工程学院高分子研究所,广东广州510275

出　　处：《癌症》2006年第12期1459-1463,共5页Chinese Journal of Cancer

基　　金：国家高科技计划(863)基金资助项目(No.2002AA214061);广东省自然科学基金资助项目(No.2003A031700);广州市科委基金资助项目(No.2004Z3-D2011)~~

摘　　要：背景与目的:生物可降解载药纳米微粒作为新型药物靶向传输和缓释/控释载体,可延长药物的生物半衰期,减轻药物的毒副作用,而且具有良好的生物相容性。本实验制备可生物降解的载5-氟尿嘧啶(5-fluorouracil,5-FU)葡聚糖接枝聚乳酸共聚物(5-FU/DEX-g-PLA),探讨其对人肝癌细胞HepG2的体内外杀伤作用。方法:利用分子自组装技术制备5-FU/DEX-g-PLA载药纳米微粒,透射电镜观察纳米粒形态,分光光度法计算载药率,MTT法观察对HepG2细胞的体外杀伤作用,动物实验观察其体内抑瘤效应。结果:5-FU/DEX-g-PLA纳米微粒呈球形,粒径约50nm,药物包封率约9.3%。体内药物代谢动力学数据显示,5-FU纳米制剂在血液中维持时间长于5-FU裸药;MTT结果显示,5-FU纳米组细胞生长抑制率(58.8%)与5-FU裸药组(58.0%)差异无显著性(P>0.05);体内抑瘤实验显示,5-FU纳米组肿瘤抑制率(73.1%)显著高于5-FU裸药组(57.5%)。结论:5-FU/DEX-g-PLA纳米微粒可有效抑制肝癌细胞的生长。BACKGROUND ＆ OBJECTIVE. Biodegradable colloidal nano- micelles is a novel targeting drug delivery and controlled release system, which could prolong the biological half-life and lighten the toxicity of chemotherapeutant, meanwhile, present fine biocompatibility. This study was to prepare the biodegradable 5-fluorouracil （5-FU）/DEX-g-PLA nano-micelles, and investigate their killing effect on hepatocarcinoma cell line HepG2 in vitro and in vivo. METHODS： 5-FU/DEX-g-PLA nano-micelles were prepared by ＂self-assembly＂. Its morphology was observed by transmission electron microscopy. The encapsulating efficiency of 5-FU was determined by ultraviolet spectrophotometry. The in vivo releasing of 5-FU from nano-micelles was investigated by high-performance liquid chromatography （HPLC）. The inhibitory effect of 5-FU/DEX-g-PLA on HepG2 cells in vitro was measured by MTT assay. RESULTS： 5-FU/DEX-g-PLA nano-micelles were round or elliptical; the diameter was about 50 rim. The encapsulating efficiency was about 9.3%. The concentration of 5-FU released from 5-FU/DEX-g-PLA nanomicelles was sustained for longer time than that of the naked drug. The in vitro inhibition rate of cell growth was similar in 5-FU/DEX-g-PLA group and naked 5-FU group （58.8% vs. 58.0%, P〉0.05）; the in vivo inhibition rate of tumor growth was significantly higher in 5-FU/DEX-g-PLA group than in naked 5-FU group （73.1% vs. 57.5%, P〈0.05）. CONCLUSION： 5-FU/DEX-g-PLA nano-micelles can effectively inhibit the growth of HepG2 cells.

关 键 词：5-氟尿嘧啶 接枝共聚物 纳米 肝癌细胞HEPG2 抑瘤效应 

分 类 号：TQ460.1[化学工程—制药化工]