聚乳酸包载5-氟尿嘧啶靶向超微粒子对人胃癌转移瘤的靶向性和控制释放研究

使用w／o／w复乳法制备聚乳酸载5-氟尿嘧啶超微粒子，使用透射电镜、激光粒度仪和紫外分光光度计对超微粒子进行表征，并考察其体外释药性质。将^99mTc标记的连有VEGF121单克隆抗体的超微粒子通过尾静脉注射到SCID裸鼠体内，观察它对胃癌转移瘤的靶向效果和治疗效果。结果显示超微粒子成圆球形，平均粒径为195.2nm，多分散系数为0.148，靶向载药超微粒子的载药率为8．23％，包封率为24．71％。聚乳酸载5-Fu超微粒子在PBS缓冲溶液中具有较好的控释效果，累积释放量Q与时间平方根t^1/2基本呈线性关系．尾静脉注射靶向超微粒子两小时以后可看到大部分超微粒子集中到肿瘤部位。在所有的实验组中，含5-Fu靶向载药超微粒子组的疗效最好，说明本靶向载药超微粒子具有抑制肿瘤的血管生成并在肿瘤组织释放化疗药物抑制肿瘤生长的双重作用。

Study of Targeting and Controlled Release Behavior of 5-Fluorouracil-loaded PLA Ultramicron on the Treatment of Human Gastric Tumor Xenograft

5-FU-loaded PLA ultramicron were prepared by a w/o/w emulsion evaporation method,and were characterized by transmission electron microscopy(TEM),particle size analyzer and UV spectrometer.The release performances of 5-FU loaded PLA ultramicron in vitro were studied.The VEGF/5-FU loaded PLA ultramicron labeled technetium-99m were injected in nude mice by tail vein to observe targerting effect and therapeutic effect.TEM observation showed ultramicron were spherical,The mean diameter was 195.2nm,and the index of polydispersity was 0.148, the drug content was 8.23%,and the encapsulation efficiency was 24.71%.There was a linear relationship between the amount of accumulative release Q and time square root t~(1/2).After targeted 5-FU loaded PLA ultramicron injection 2 hours,the majority of ultramicron centralized at tumor site.In all the treatment groups,5-FU/VEGF loaded PLA ultramicron group had best result.That demonstrated 5FU/VEGF loaded PLA ultramicron had multiple function with inhibition of growth of blood vessel of tumor and controlled release drug in the tumor site.