5-氟尿嘧啶的聚乙二醇-聚乳酸的胶束制备及其体外释药研究  

Study on the preparation and release behavior of 5-fluorouracil-polyethyleneglycol-polylactide polymeric micelles in vitro

作　　者：庞国棉[1] 朱亮[1] 李远达[1] 

机构地区：[1]广东药学院药科学院,广东广州510006

出　　处：《广东药学院学报》2011年第2期116-120,共5页Academic Journal of Guangdong College of Pharmacy

摘　　要：目的通过化学结合法将药物5-氟尿嘧啶(5-FU)与聚乙二醇-聚乳酸(mPEG-PLA)相连接,制备mPEG-PLA-5-FUA含药聚合物胶束,考察其体外释放性能。方法在5-FU的N-1位引入乙酸基,通过DCC缩合法,使5-氟尿嘧啶-1-基乙酸(5-FUA)与mPEG-PLA反应,制得含药聚合物mPEG-PLA-5-FUA,用红外吸收光谱(IR)、差热分析法(DTA)验证其结构;采用透析法制备聚合物胶束,分别用透射电镜观察聚合物胶束的形态,激光散射法测定聚合物胶束的粒径,紫外-可见分光光度法计算胶束载药量,芘探针荧光法测定临界胶束浓度(CMC)值,转篮法测定胶束释放度。结果经IR、DTA鉴定,成功合成了mPEG-PLA-5-FUA聚合物;其胶束平均粒径为42.1 nm,能明显看到胶束的球形核-壳结构;载药量为1.83%,CMC为2.68μg.mL-1,24 h释药量达28.7%。结论 mPEG-PLA-5-FUA载药聚合物胶束具有一定的缓释作用,有利于5-FU的抗肿瘤作用。Objective To investigate the preparation and release behavior of 5-fluorouracil- polyethyleneglycol-polylactide （mPEG-PLA-5-FUA） polymeric micelles in vitro with 5-fluorouracil active ester and polyethyleneglycol-polylactide（mPEG-PLA） by chemical bonding method. Methods Acetic acid was conjugated to N-1 of 5-FU. Then 5-fluorouacil-l-yl-acetic acid was connected with mPEG-PLA block copolymer through DCC chemical reaction to obtain mPEG-PLA-5-FUA polymeric micelles. The structure was identified by IR, DTA, The polymeric mieelles were prepared by diafiltration, and the morphology was observed by transmission electron microscope and the particle size was examined by dynamic light scattering; The drug loading encapsulation were determined by UV. The critical micelle concentration （CMC） was detected with fluorescence method with pyrene as a probe. The release of the 5-FU loaded mPEG-PLA micelles in vitro was evaluated using a dialysis method. Results The mean diameters of the micelles were 42.1 nm. Pictures by transmission electron microscopy revealed spherical and core-shell 5- FU loaded mPEG-PLA micelles. The drug-loading rate was 1.83% ,and the CMC were 2.68 μg · mL^-1, and the release of the micelles were 28.7% after 24h. Conclusions The mPEG-PLA-5-FUA polymeric mieelles can be used as a new carrier for sustained release drug systems, which is beneficial to the anti- tumor activity of 5-FU.

关 键 词：5-氟尿嘧啶 聚乙二醇-聚乳酸 聚合物胶束 

分 类 号：R944[医药卫生—药剂学]