依托泊苷植入剂治疗小鼠Lewis肺癌的药效学研究

发布时间：2018-12-18 20:25

【摘要】：目的:比较依托泊苷(VP-16)植入剂与VP-16注射液对小鼠Lewis肺癌的抑瘤效果、局部复发及全身毒性的影响,探究VP-16植入剂局部化疗相对于VP-16注射液的优势。方法:⑴熔融挤出法制备VP-16植入剂,并采用高效液相法(HPLC)检测VP-16植入剂的体内外释放度;⑵通过注射LLC细胞悬液建立小鼠皮下移植瘤模型,比较VP-16植入剂与VP-16注射液对小鼠肿瘤的抑制作用及其对荷瘤小鼠生存期、体重和脏器指数的影响;⑶通过注射LLC肿瘤组织悬液建立小鼠局部复发模型,考察局部植入VP-16植入剂和腹腔注射VP-16注射液对小鼠肿瘤局部复发、骨髓抑制以及肝脏损伤的区别。结果:自制VP-16植入剂含药量为37.62%,体内外释放周期均可超过15天。与腹腔注射VP-16相比,VP-16植入剂能显著抑制小鼠皮下肿瘤的生长,延长小鼠生存期,并对小鼠体重及脏器指数无显著影响,其中植入剂高剂量(2.4 mg)组的治疗效果最为显著,抑瘤率达到70.96%(p0.001),生存期延长率超过100%。另外,局部植入VP-16植入剂能显著抑制小鼠肿瘤局部复发,降低VP-16的骨髓抑制和肝脏损伤等毒副作用。结论:VP-16植入剂用于小鼠局部化疗可显著提高药物疗效,并降低全身毒副作用。
[Abstract]:Objective: to compare the effect of etoposide (VP-16) implantation and VP-16 injection on tumor inhibition, local recurrence and systemic toxicity of Lewis lung cancer in mice. Methods: (1) VP-16 implants were prepared by melt extrusion, and the in vitro and in vivo release of VP-16 implants were measured by high performance liquid phase (HPLC). 2Infusion of LLC cell suspensions to establish subcutaneous transplanted tumor model in mice, the inhibitory effect of VP-16 and VP-16 injection on tumor and the effects on survival time, body weight and organ index of mice bearing tumor were compared. 3The local recurrence model of mice was established by injecting LLC tumor tissue suspension, and the difference between local implantation of VP-16 implant and intraperitoneal injection of VP-16 injection on tumor recurrence, bone marrow suppression and liver injury in mice was investigated. Results: the content of VP-16 implant was 37.62%, and the release period in vivo and in vitro could exceed 15 days. Compared with intraperitoneal injection of VP-16, VP-16 implantation could significantly inhibit the growth of subcutaneous tumor in mice, prolong the survival time of mice, and had no significant effect on the body weight and organ index of mice. In the high dose group (2. 4 mg), the therapeutic effect was the most significant, the tumor inhibition rate was 70.96% (p0. 001), and the survival rate was more than 100%. In addition, local implantation of VP-16 could significantly inhibit the local recurrence of tumor in mice and reduce the side effects of VP-16, such as bone marrow suppression and liver injury. Conclusion: local chemotherapy with VP-16 implantation can significantly improve the efficacy of the drug and reduce systemic side effects.
【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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