【摘要】：目的:比較依托泊苷(VP-16)植入劑與VP-16注射液對小鼠Lewis肺癌的抑瘤效果、局部復發(fā)及全身毒性的影響,探究VP-16植入劑局部化療相對于VP-16注射液的優(yōu)勢。方法:⑴熔融擠出法制備VP-16植入劑,并采用高效液相法(HPLC)檢測VP-16植入劑的體內外釋放度;⑵通過注射LLC細胞懸液建立小鼠皮下移植瘤模型,比較VP-16植入劑與VP-16注射液對小鼠腫瘤的抑制作用及其對荷瘤小鼠生存期、體重和臟器指數(shù)的影響;⑶通過注射LLC腫瘤組織懸液建立小鼠局部復發(fā)模型,考察局部植入VP-16植入劑和腹腔注射VP-16注射液對小鼠腫瘤局部復發(fā)、骨髓抑制以及肝臟損傷的區(qū)別。結果:自制VP-16植入劑含藥量為37.62%,體內外釋放周期均可超過15天。與腹腔注射VP-16相比,VP-16植入劑能顯著抑制小鼠皮下腫瘤的生長,延長小鼠生存期,并對小鼠體重及臟器指數(shù)無顯著影響,其中植入劑高劑量(2.4 mg)組的治療效果最為顯著,抑瘤率達到70.96%(p0.001),生存期延長率超過100%。另外,局部植入VP-16植入劑能顯著抑制小鼠腫瘤局部復發(fā),降低VP-16的骨髓抑制和肝臟損傷等毒副作用。結論:VP-16植入劑用于小鼠局部化療可顯著提高藥物療效,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.
【學位授予單位】：合肥工業(yè)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R965

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