同载基因和药物的超微载体粒子的制备及体外评价  

Construction and in vitro Evaluation of 5-Fluorouracil-and Gene-loaded PLGA/O-CMC Nanoparticles

作　　者：胡云霞[1] 原续波[1] 康春生[1] 郭毅[1] 常津[1] 

机构地区：[1]天津大学材料科学与工程学院纳米生物技术研究所,天津300072

出　　处：《高分子通报》2004年第4期69-73,共5页Polymer Bulletin

基　　金：国家重大基础研究 ( 973 )项目前期研究专项基金 ( 2 0 0 1CCC0 1 40 0 ) ;天津市科委重点基金资助项目( 0 1 3 61 661 1 ) ;国家自然科学基金 ( 5 0 3 73 0 3 3 )

摘　　要：以聚乳酸_乙醇酸共聚物 (PLGA)和自行制备的O_羧甲基壳聚糖 (O_CMC)为原料 ,以 5_氟尿嘧啶 (5 Fu)为抗癌药物模型 ,以反义EGFR(表皮生长因子受体 )为基因药物模型 ,构建与评价了同载抗癌药物与基因的复合功能纳米药物载体系统。同载超微粒子的平均粒径为 2 5 8 7nm ,粒径分布指数为 0 14 2 ,粒子表面 ξ电位为 - 10 6 7eV。同载超微粒子在PBS中的释药行为研究表明 :超微粒子中 5_FU和基因均具有零级缓慢释放特性。体外肿瘤细胞存活率实验和免疫组化实验均证实同载超微粒子能高效抑制TJ90 5人脑胶质瘤细胞的增殖。最后用荧光共聚焦显微镜动态监测了超微粒子进入瘤细胞的转染过程 ,发现粒子可在不同时间内进入细胞浆和细胞核。Fluorouracil (5-FU) and antisense-EGFR cDNA loaded nanoparticles were prepared by improved W/O/W method using poly (D,L-lactide-co-glycolic acid) (PLGA) and O-carboxymethyl chitosan (\%O\%-CMC) due to their attractive degradation and physicochemical properties,and this multiple-functional drug delivery system can realize the combination effect of anticancer drug and gene in the therapy of diseases. The results of characterizing these nanoparticles showed that: the mean size,polydispersity and Zeta potenial of 5-FU-encapsulated PLGA/\%O\%-CMC NPs while absorbing antisense-EGFR was 258.7nm,0.142,and -10.67eV,respectively. The release behavior of 5-FU and gene from NPs was coincidence with Zero-level release. Gliomas cell viability in vitro as well as immunohistochemical staining demonstrated that these nanoparticles had high cytotoxicity on gliomas cells TJ905. Fluorescence confocal microscope was used to trace the procedures of cell transfection induced by nanoparticles. It was found that nanoparticles were both in cytoplasma and nucleus after 24h.

关 键 词：O-羧甲基壳聚糖 聚乳酸-乙醇酸共聚物 同载超微粒子 抗癌药物 基因治疗 制备 体外评价 纳米药物载体系统 

分 类 号：TQ460[化学工程—制药化工]