靶向熊果酸脂质体的体内分布及其对裸鼠移植瘤的治疗作用

发布时间：2018-12-12 14:32

【摘要】：目的研究叶酸受体靶向性熊果酸脂质体的体内组织分布及肿瘤靶向作用。方法以叶酸靶向材料叶酸-聚乙二醇-胆固醇的半琥珀酸盐作为靶向分子,再用聚乙二醇-二硬脂酰磷脂酰乙醇胺(m PEG-DSPE)对脂质体表面进行结构修饰,利用薄膜分散法制备长循环脂质体(F-PEG-L-UA);测定裸鼠心、肝、脾、胃、肾及肿瘤组织的药物含量,考察熊果酸体内的分布差异,比较叶酸受体靶向作用和单纯给药在组织分布的不同;并构建裸鼠口腔癌皮下移植瘤模型观察F-PEG-L-UA对裸鼠口腔癌的抑制作用。结果与游离熊果酸相比,熊果酸脂质体明显增加药物在体内长循环的时间,在肝、肾和肿瘤组织中药物浓度明显高于其他组织,说明熊果酸集中分布于肝脏和肾脏进行代谢,并且具有良好的肿瘤靶向性。F-PEG-L-UA与其他各组相比较,肿瘤生长受到明显抑制,其瘤体积减少约50%(P0.05);而游离熊果酸和非靶向组的瘤体积没有得到有效控制。结论本实验制备的F-PEG-L-UA具备高效的肿瘤靶向性,是一种有效的抗肿瘤药物传递系统。
[Abstract]:Objective to study the tissue distribution and tumor targeting effect of folate receptor-targeted ursolic acid liposomes. Methods the surface of liposomes was modified by poly (ethylene glycol) -dicarbonyl ethanolamine (m PEG-DSPE), a folic acid targeting material, was used as the target molecule. Long cycle liposomes (F-PEG-L-UA) were prepared by thin-film dispersion method. The contents of drugs in heart, liver, spleen, stomach, kidney and tumor tissue of nude mice were determined, and the distribution of ursolic acid in vivo was investigated. To observe the inhibitory effect of F-PEG-L-UA on oral carcinoma in nude mice. Results compared with free ursolic acid, ursolic acid liposome significantly increased the time of drug circulation in vivo, and the concentration of ursolic acid in liver, kidney and tumor tissues was significantly higher than that in other tissues, indicating that ursolic acid was mainly distributed in liver and kidney for metabolism. Compared with other groups, the tumor growth of F-PEG-L-UA was significantly inhibited, and the tumor volume was reduced by about 50% (P0.05). The tumor volume of free ursolic acid and non-target groups was not effectively controlled. Conclusion the F-PEG-L-UA prepared in this study has high tumor targeting and is an effective antitumor drug delivery system.
【作者单位】：江汉大学医学院;华中科技大学同济医学院药学院;
【基金】：国家自然科学基金资助项目(81072596)
【分类号】：R965

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