阿霉素-N-乳糖酰壳聚糖-丝素蛋白微球的制备以其兔体内药效学的研究

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目的:制备阿霉素-N-乳糖酰壳聚糖-丝素蛋白微球(adriamycin-N-chitosan-silk fibroin-microspheres,ADR-N-CS/SF-MS),并观察其对兔VX2肝移植瘤的化疗栓塞术后抑瘤作用。方法:采用乳化凝胶化法制备ADR-N-CS/SF-MS;24只新西兰大白兔经超声引导下于肝脏左叶植入VX2肿瘤组织块,建立肝移植瘤模型,并随机分为4组,即A组为每组6只股动脉穿刺插管经肝动脉分别给予ADR-N-CS/SF-MS(治疗组),B组为N-CS/SF-MS(对照组),C组为碘化油+ADR溶液,D组为0.9%氯化钠液;经治疗后,观察各组兔血常规及肝、肾功能和肝肿瘤体积的动态变化以及用CT成像法分析其治疗前后肝肿瘤影像学的改变。结果:各组动物血细胞数量及血红蛋白值均有不同程度下降,治疗组动物术后平均白细胞数量(中性粒细胞为主)增多,肝功能均出现一过性损害;治疗30d(A,B,C组)疗效与D组相比,其肿瘤体积明显减小(P<0.01),其中A组肿瘤体积缩小较B,C两组明显(P<0.01),而B,C两组的肿瘤体积均值间比较,差异无统计学意义(P>0.05);A,B,C各组抑瘤率分别为87.23%,62.98%和56.02%;经CT检查示其病灶液化坏死,强化不明显。结论:ADR-N-CS/SF-MS制备工艺简单易行,其治疗组抑制肿瘤生长较为明显(P<0.01),以致肿瘤缩小或坏死。 Objective: To prepare adriamycin-N-chitosan-silk fibroin-microspheres (ADR-N-CS / SF-MS) The antitumor effect of transplanted tumor after chemotherapy and embolization. METHODS: ADR-N-CS / SF-MS was prepared by emulsification-gelation method. Twenty-four New Zealand white rabbits were implanted with VX2 tumor tissue blocks on the left lobe of the liver under ultrasound guidance. Liver xenograft models were established and randomly divided into 4 groups Group A was treated with ADR-N-CS / SF-MS (treatment group), N-CS / SF-MS Group was iodized oil + ADR solution and group D was 0.9% sodium chloride solution. After treatment, the changes of blood routine, liver and kidney function and liver tumor volume in each group were observed and the changes of liver tumor volume before and after treatment were analyzed by CT imaging Liver tumor imaging changes. Results: The number of hemocytes and hemoglobin in each group decreased in varying degrees. After treatment, the average number of leukocytes (mainly neutrophils) and the transient damage of liver function in the treated group were significantly higher than those in the untreated group. After treatment for 30 days (A, B, (P <0.01). The volume of tumor in group A was smaller than that in group B and C (P <0.01), while the volume of tumor in group B and C The difference was not statistically significant (P> 0.05). The inhibitory rates of A, B and C in each group were 87.23%, 62.98% and 56.02% respectively. CT showed that the lesions were liquefied and necrotic, but the enhancement was not obvious. Conclusion: The preparation process of ADR-N-CS / SF-MS is simple and easy, and its treatment group significantly inhibited tumor growth (P <0.01), resulting in tumor shrinkage or necrosis.
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