去甲斑蝥素-泊洛沙姆407缓释制剂局部注射治疗肿瘤的实验研究

Experimental Study on Intratumoral Administration with Sustained-Release Preparation of Norcantharidin-Poloxamer 407

目的:探讨增强去甲斑蝥素的抗癌效果,减轻其毒副反应。方法:选择泊洛沙姆407作为去甲斑蝥素局部用药的载体,将去甲斑蝥素制成缓释剂型,比较不同剂型去甲斑蝥素的毒性及对荷 W(256)肿瘤大鼠的抗肿瘤效果。结果:(1)去甲斑蝥素缓释剂型的毒性明显低于单纯去甲斑蝥素;(2)去甲斑蝥素缓释剂型治疗组大鼠肿瘤生长受到显著抑制,肿瘤组织坏死广泛,治疗后平均生存期延长(与单纯去甲斑蝥素比较,P<0.05);综合疗效优于单纯去甲斑蝥素组。结论:去甲斑蝥素-泊洛沙姆407缓释制剂瘤内注射,通过延缓药物释放,保持肿瘤内有效药物浓度,并避免峰值血药浓度出现而起到增效减毒作用。

Objective:To enhance therapeutic effects and reduce adverse effects of norcantharidin (NCFD) on anti-tumor. Methods:Poloxamer 407 (P407) gel was used as a sustained-release vehicle for topical administration of NCTD.The tox- icity of different preparations of NCTD in mice were observed,respectively.The anti-tumor effects of NCTD or NCTD in P407 (NCTD/P) on SD rats implanted with W_(256) carcinoma were also studied.Results:(1) The toxicity of the sus- tained-release preparation of NCTD in P407 gel was lower than that of free NCTD.(2) There were significantly slower tumor growth,more extensive tumor necrosis and longer survival time in SD rats treated with NCTD/P than those treated with free NCTD.Conclusion:The NCTD in P407 gel appeared to be less toxic and have more tumoricidal effects than that equivalent dose of free NCTD,mainly because NCTD in P407 might stay in the injected location for a longer time and produce a lower peak level in plasma than free NCTD.