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

Studies on Preparation of Adriamycin-N-chitosan/silk Fibroin-microspheres and Its Tumor Inhibitory Effect

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）and to in- vestigate their efficacy on hepatic embolization in a rabbit model bearing VX2 liver tumor. Methods： ADR-N-CS/ SF-MS were achieved by emulsification cross-linking process. Twenty-four New Zealand rabbits were randomly divided into 4 groups（n=6）,and the tissues of VX2 carcinoma were implanted in the left lobes of the livers under the guidance of ultrasonic. Transcatheter arterial chemoembolization（TACE） was performed by ADR-N-CS/SF-MS as Group A, blank N-CS/SF-MS as Group B, Lipiodol-ADR as Group C respectively, and a control group as Group D. All procedures were by right femoral artery access. Blood sampling and CT imaging were performed during the 30-day follow up while the tumor size was also recorded. Results： In all groups, there was a decrease in the mean number of red blood cells and hemoglobin. An increase in the mean leukocyte count and polymorphonuclear cell count was observed in groups A, B and C. Temporary elevation of the serum ALT, AST levels was observed but reversed within two weeks. Bun and Cr showed no significant changes. Thirty days after treatment, the tumor sizes of Group A, B and C were significantly decreased（P〈0.01）compared with the saline control group. The tumor sizes of Group A was also significantly decreased（P〈0.01）compared with Group B and C while it showed no significant difference（P〉0.05） between Group B and C. The tumor inhibition rates（IR） were 87.23%, 62.98% and 56.02%, respectively for Group A, B and C. The tu- mors demonstrated as low density, well discernible from the surrounding liver tissue with internal lower density uneven necrosis areas on plain CT scan with inconspicuous enhancement on arterial phase image. Conclusion： ADR-N-CS/ SF-MS were well prepared.The tumor growth rate was decreased significantly（P〈0.01）in ADR-N-CS/SF-MS group. This novel microsphere can result in tumor necrosis.