5-FU核-壳型共聚物纳米胶束的制备及其体内释药的研究  

Studies on 5- FU/PEG-PBLG Nano-micelles:Preparation, Characteristics,and Drug Releasing In Vivo

作　　者：李苏[1] 姜文奇[1] 王安训[2] 管忠震[1] 潘仕荣[3] 

机构地区：[1]中山大学肿瘤防治中心内科,广东广州510060 [2]中山大学附属第一医院口腔科,广东广州510080 [3]中山大学附属第一医院心内科,广东广州510080

出　　处：《癌症》2004年第4期381-385,共5页Chinese Journal of Cancer

基　　金：广东省自然科学资金(No.021865;021809)~~

摘　　要：背景与目的:5-氟尿嘧啶(5-FU)属抗代谢类的抗癌药,其在体内半衰期仅为5min,临床上为了维持长时间的稳态浓度,往往采取持续静脉滴注(48h、72h、28d)的给药方式,因此,有必要开发新型5-FU缓释制剂。本研究的目的是探讨两亲嵌段共聚物聚乙二醇-聚谷氨酸苄酯(PEG-PBLG)为载体的5-FU核-壳型缓释型纳米胶束的制备、形态特征及体内释药特性。方法:用阴离子聚合法制备PEG-PBLG纳米聚合物;透析法制备5-FU纳米胶束;透射电镜、扫描电镜观察5-FU胶束形态;紫外分光光度法测定载药量;高效液相色谱法检测5-FU纳米胶束在体内的释药特性。结果:PEG-PBLG包裹的5-FU纳米胶束呈圆形或椭圆形,直径约为180～250nm,中间药库区大小约为200nm,周围亲水区厚度约为30nm,载药量为(29.500±0.015)%。5-FU对照组在体内呈一室模型,半衰期(t1/2)仅为5.3min,最高浓度(Cmax)17047.3μg/L,峰浓度时间(Tmax)为给药后即刻,浓度-时间曲线下面积(AUC)为6263.7μg/(L·min);而5-FU/PEG-PBLG纳米胶束注射入体内后呈典型的纳米胶束释药模型即突释-缓释模型,t1/2为63.2min,Cmax为4563.5μg/L,Tmax为1.25h,AUC为5794.5μg/(L·min)。5-FU/PEG-PBLG纳米胶束比普通的5-FU制剂Tmax长(P<0.01),Cmax较低(P<0.01),t1/2较长(P<0.01)。BACKGROUND & OBJECTIVE: 5- Fluorouracil (5- FU) belongs to an timetabolic anticancer drugs and its half- life time in vivo is only about 5 mi nutes. Continuous infusion (48 hours,72 hours,28 days) was commonly used to main tain long- time steady- state concentration (Css). So it is necessary to explo it new slow- release system for 5- FU. This article was designed to investigat e the preparation technique,shape characteristics,and drug releasing characteri - stics in vivo of 5- FU loaded core- shell type nanoparticles which were ma de by biodegradable amphiphlic poly (ethylene glycol)- poly (γ - benzyl- L- glutamate)(PEG- PBLG). METHODS: The PEG- PBLG nano- micelles were prepared b y diafiltration method. Its morphology was observed by transmission electron mic roscopy and scan electron microscopy. Encapsulating efficiency of 5- FU was det ermined by ultraviolet spectrophotometry. The 5- FU releasing characteristics f rom nano- micelles in vivo were investigated by high- performance liquid chrom atography (HPLC). RESULTS: 5- FU loaded PEG- PBLG copolymer nano- micelles ( 5- FU/PEG- PBLG) was of round or ellipsic shape. The diameter of the micelles was 180- 250 nm; the size of drug storeroom was about 200 nm and the thickness of hydrophilic zone was about 30 nm. The entrapment efficiency was (29.5± 0.015 )% . In control group, 5- FU is one- compartment in vivo; its half- life was 5.3 minutes; the maximum plasma concentration (Cmax) was 17047.3 μ g/L;Tmax wa s the time of attaining Cmax of the end of infusion; the area under the plasma c oncentration- time curve (AUC) was 6263.7 μ g/L· min. However, the model of n ano- micelles in vivo was typical release- drug of nano- micelles namely abr upt release- slow release; its t1/2 was 63.2 minutes; Cmax was 4563.5 μ g/L;Tm ax was 1.25 hours;AUC was 5794.5 μ g/L· min. Compared with 5- FU preparation, Tmax of 5- FU/PEG- PBLG was longer (P< 0.01);Cmax was lower (P< 0.01);t1/2 wa s longer (P< 0.01);AUC was similar (P >0.01). CONCLUSION: The 5- FU/PEG- PBLG

关 键 词：5-FU 核-壳型共聚物 纳米胶束 制备方法 体内释药 5-氟尿嘧啶 给药方式 抗癌药 

分 类 号：R944[医药卫生—药剂学]