甲氨蝶呤缓释植入剂对S180肉瘤小鼠的药效学研究

发布时间：2018-01-19 08:46

本文关键词： 癌症甲氨蝶呤缓释植入剂复发肉瘤抑瘤率　出处：《合肥工业大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:制备甲氨蝶呤缓释植入剂,检测其体外降解度,以及体外、内释放度。研究其延迟小鼠肉瘤局部复发的作用以及对s180肉瘤药效学研究,探讨与传统给药方式相比其优势。方法:1)以PLGA和PEG4000为辅料,采用熔融挤出法制备甲氨蝶呤缓释植入剂。采用紫外光度法和高效液相色谱法分别检测其体外、内释放度以及真实含药量。2)于昆明小白鼠腋下皮下注射Sarcoma 180细胞,模拟术后残留病灶,建立肉瘤术后辅助化疗模型,对甲氨蝶呤缓释植入剂延迟肉瘤复发作用做出评价。3)于昆明小白鼠腋下皮下注射Sarcoma 180细胞,建立S180肉瘤模型,对甲氨蝶呤缓释植入剂抑制肿瘤生长做出评价。结果:甲氨蝶呤缓释植入剂实际含药量为8.34%±0.65,实际含量与理论含量呈一致性,在体外、内可分别达到7 d和15 d的长效释放。同剂量下,与注射液组相比,生存期中位数明显在增加,且甲氨蝶呤缓释植入剂抑瘤率高达77.06%,而甲氨蝶呤注射液抑瘤率仅30.15%。结论:甲氨蝶呤缓释植入剂可达到缓释药物的效果,与传统给药方式相比甲氨蝶呤缓释植入剂能更有效地延迟肿瘤复发且抑制肿瘤生长,同时延长了小鼠的生存期。
[Abstract]:Objective: to prepare a sustained-release methotrexate implant and to detect its degradation in vitro and its release in vitro and to study the role of MTX in delaying the local recurrence of sarcoma in mice and its pharmacodynamic study on S180 sarcoma. To explore the advantages of traditional drug administration method: 1) PLGA and PEG4000 were used as adjuncts. Methotrexate sustained-release implants were prepared by melt extrusion method. UV spectrophotometry and high performance liquid chromatography (HPLC) were used to detect methotrexate in vitro. Sarcoma 180 cells were injected subcutaneously into Kunming mice subaxillary to simulate the residual lesions and to establish the model of adjuvant chemotherapy after sarcoma operation. To evaluate the delayed recurrence effect of methotrexate (MTX) implants. 3) to establish S180 sarcoma model by subaxillary injection of Sarcoma 180 cells in Kunming mice. Results: the actual content of methotrexate sustained-release implants was 8.34% 卤0.65, which was consistent with the theoretical content in vitro. The median survival time was significantly higher than that in the injection group, and the tumor inhibition rate of MTX was as high as 77.06%. The inhibition rate of methotrexate injection was only 30.15. Conclusion: methotrexate sustained-release implant can achieve the effect of sustained-release drug. Compared with traditional administration methotrexate sustained-release implants can delay tumor recurrence and inhibit tumor growth and prolong survival time of mice.
【学位授予单位】：合肥工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R965

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