甲氨蝶呤缓释植入剂延迟小鼠肉瘤复发的研究

发布时间：2019-02-19 12:35

【摘要】：目的:制备甲氨蝶呤缓释植入剂,检测其体外降解以及体外、内释放度。研究其延迟小鼠肉瘤局部复发的作用,探讨与传统给药方式相比的优势。方法: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、体内释放度以及真实含药量。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。结果:采用熔融挤出法成功制备了甲氨蝶呤缓释植入剂,其实际含药量为(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和15 d的长效释放。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,同时延长了小鼠的生存期。结论:熔融挤出法可成功制备甲氨蝶呤缓释植入剂,将有利于延迟肿瘤局部复发的治疗效果。
[Abstract]:Aim: to prepare methotrexate sustained-release implant and to detect its degradation in vitro and its release in vitro. To study the effect of delayed local recurrence of sarcoma in mice and to explore the advantages compared with traditional administration. Methods: methotrexate sustained-release implants were prepared by melt extrusion with PLGA and PEG4000 as excipients. Ultraviolet spectrophotometry and high performance liquid chromatography were used to determine its release in vitro and in vivo. Sarcoma 180 cells were injected subcutaneously into Kunming mice. The residual lesions were simulated and the model of adjuvant chemotherapy was established to evaluate the delayed recurrence of sarcoma with methotrexate sustained-release implants. Results: methotrexate sustained-release implants were successfully prepared by melt extrusion. The actual content of methotrexate was (8.34 卤0.65)%, which was consistent with the theoretical content. In vitro, the release of methotrexate could reach 7 days and 15 days, respectively. Compared with traditional administration methotrexate sustained-release implants could delay tumor recurrence and prolong survival of mice. Conclusion: methotrexate sustained-release implants can be successfully prepared by melt extrusion, which will be helpful to delay the local recurrence of tumor.
【作者单位】：合肥工业大学生物与医学工程学院;
【基金】：国家自然科学基金面上项目(21672050)
【分类号】：R965

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