【作者】 李学明； 徐元龙； 陈国广； 韦萍；

【Author】 LI Xue-ming*,XU Yuan-long,CHEN Guo-guang,WEI Ping College of Life Science and Pharmaceutical Engineering,Nanjing University of Technology,Nanjing 210009,China

【机构】 南京工业大学制药与生命科学学院；

【摘要】 目的:以生物可降解材料乳酸-乙醇酸共聚物(PLGA)制备氟尿嘧啶(FU)纳米粒,并对纳米粒的形态特征和体内外释放特性进行研究。方法:采用复乳化-溶剂挥发法结合高压均质法制备5-FU-PLGA纳米粒。用透射电镜观察纳米粒的形态,并对5-FU-PLGA纳米粒的粒径及其分布,载药量,包封率,体内外释药进行了研究。结果:制得的5-FU-PLGA纳米粒为类球形实体粒子,平均粒径为85.4nm,载药量为10.6%,包封率为52.7%,体外释药符合Higuchi方程:Q=5.8516t1/2+8.735(r=0.9923)。5-FU水溶液组在体内半衰期(t1/2)仅为0.36h,峰浓度时间(Tmax)为0.26h,浓度-时间曲线下面积(AUC)为18.15h·μg/ml,而同剂量的5-FU-PLGA纳米粒在体内t1/2为2.35h,Tmax为1.13h,AUC为41.09h·μg/ml,结论:制得的5-FU-PLGA纳米粒可改变5-FU体内的药物动力学行为,延长5-FU在体内的循环时间,具有明显的缓释作用,口服吸收好,生物利用度有明显提高。更多还原

【Abstract】 Aim: To prepare 5-Fluorouracil(5-FU) loaded nanoparticles using the biodegradable materials- poly(L-lactic-co- glycolic acid)(PLGA), and to study the shape characteristics and releasing behavior of the nanoparticles in vitro and in vivo. Methods: 5-FU loaded nanoparticles(NPs) were made by double emulsion(W/O/W)-liquid drying process with PLGA as carrier materials. In order to reach submicron size, we used a high pressure homogenizer with a view to obtaining NPs with a very high grade of monodispersity. The shape of the nanoparticles was observed by TEM. The mean diameter and the size distribution of nanoparticles were determined by photon correlation spectrometry, the drug loading, the incorporation efficiency and releasing behavior of 5-FU-PLGA-NPs in vitro were examined by ultraviolet spectrophotometry. The 5-FU releasing characteristics in vivo were investigated by high-performance liquid chromatography(HPLC) method after administration by intragastric(ig) route. Results: 5-fluorouracil PLGA nanoparticles were sphere like with the mean size of 85.4 nm, the drug loading was 10.6%, the encapsulation efficiency of nanoparticles was 52.7%. The in vitro release behavior could be expressed by the Higuchi’s equation: Q=5.8516t1/2+8.735(r=0.9923). 5-FU solution and 5-FU-PLGA-NPs in vivo were fitted a two-compartment model. In control group, The half life (t1/2) of 5-FU solution was 0.36 h, Tmax was 0.26 h, the area under the plasma concentration-time curve(AUC) was 18.15 h·μg /ml; Compared with 5-FU solution, t1/2 of 5-FU-PLGA-NPs was 2.35 h, Tmax was 1.13 h, AUC was 41.09 h·μg /ml. Conclusion: 5-FU can be encapsuled in PLGA-nanoparticles and the 5-FU-PLGA-NPs showed significant sustained release in vivo, and 5-FU-PLGA-NPs can change the pharmacokinetics of 5-FU,prolong the circulation time in vivo and make a slow release.更多还原