载5-FU纳米微粒抗肿瘤的实验研究

目的： 研究抗癌药5-FU纳米控释静脉注射微粒的制备工艺及其体内外抗肿瘤作用。方法： 以聚乳酸 (PLA)作为基质材料，采用超声乳化-溶剂挥发法制备PLA包载5-FU的纳米微粒（5-FU-NPs）。扫描电镜观察5-FU-NPs形态，通过激光光散射实验测定5-FU-NPs的粒径分布。利用高效液相色谱(HPLC)测定5-FU-NPs的载药率，以MTT方法检测5-FU-NPs体外杀伤癌细胞效应，用5-FU-NPs不同剂量、给药频度条件下体内抑瘤实验。结果： 电镜观察5-FU-NPs为表面光滑的球形微粒，粒径分布平均值是191.1 nm，呈正态分布。5-FU-NPs载药率为15.2%。体外MTT实验提示5-FU-NPs作用明显优于5-FU（P<0.05）。体内抑瘤实验表明：5-FU-NPs间隔给药疗效优于未包载药物每日给药的疗效，量-效关系明显，且毒性减低。结论： 5-FU-NPs可以作为5-FU的有效载体，实现药物控制释放并减低毒性，发挥药物更佳的抗肿瘤作用。

Experimental study of 5-fluorouracil loaded polylactic acid nanoparticles control-releasing preparation on tumor

AIM:To investigate the preparation techniques and anti-tumor effects both in vitro and in vivo of a novel nanoparticles control-releasing preparation of 5-fluorouracil(5-FU)by intravenous injection.METHODS:With polylactic acid(PLA)as marix materials,we adopted ultrasound emulsification method to prepare PLA enveloped 5-FU nanoparticles(5-FU-NPs).Scanning electricity microscopy was used to observe the morphology of 5-FU-NPs and laser optical scattering experiment was conducted to determine its diameter distribution.The drug-carrying capacity(ratio)of the nanoparticles was determined by means of high-power liquid chromatography(HPLC)and MTT test was used to observe cytotoxicity in vitro.The anti-tumor effects were determined at different dosages,frequencies of taking drugs in vivo.RESULTS:Scanning electron microscopy showed that the 5-FU-NPs were globular particles with smooth surface in an average particle diameter of 191.9 nm with a normal distribution,and the drug-carrying capacity of 5-FU-NPs was 15.2%.5-FU-NPs had the same anti-cancer effect as unenveloped drug in vitro and showed typical dose-effect relationship.Compared to naked 5-FU,5-FU-NPs presented significant difference(P<0.05)in anti-cancer effect.CONCLUSION:Nanoparticles may serve as effective carrier for controlled release of 5-FU,which lead to reasonable administration of 5-FU with less toxicity.