植入靶向持续组织间化疗概念的可行性动物实验报告  

Report on The Results of The Feasibility of Animal Experiment for The Establishment of The Concept of Implanting and Targeting Continuous Interstitial Chemotherapy

作　　者：王建[1] 陆彬[2] 林苹[3] 熊素彬[2] 陆燕蓉[3] 张洁[3] 李方[1] 尹宗宁[2] 黄孝忠[3] 

机构地区：[1]四川省肿瘤医院,成都610041 [2]四川大学华西医学中心,成都610041 [3]四川大学华西医院肿瘤中心,肿瘤研究所,成都610041

出　　处：《四川肿瘤防治》2003年第3期138-142,176,共6页Sichuan Journal of Cancer Control

基　　金：卫生部科学研究基金资助 (98- 1- 35 2 )

摘　　要：目的 :通过动物实验 ,研究提出植入靶向持续组织间化疗的概念的可行性 ,并与其他疗法比较此种疗法有何优越性。方法 :用生物相容性和可生物降解的聚乳酸作为缓释药物载体 ,制备可在体内缓释氟脲嘧啶 (Fluo rouracil,Fu)微球。采用植入被动靶向的方式 ,将氟脲嘧啶缓释微球直接植入实验动物的移植肿瘤内或肿瘤旁 ,形成局部持续的抗癌药物的高浓度 ,使Fu分子不断渗入瘤细胞内 ,以杀死肿瘤细胞。用随机分组的方式 ,对比Fu缓释微球和Fu注射剂不同的给药方式 ,测定肿瘤消退和毒副作用 ,并依据病理切片结果作定量分析 ,评价Fu聚乳酸微球的抗癌疗效。结果 :Fu聚乳酸微球有平稳持续缓释药物的理想曲线 ,没有突释效应。用被动靶向直接植入方式 ,将Fu聚乳微球直接植入实验动物的移植肿瘤病灶区域或肿瘤旁 ,比注射剂Fu全身给药 ,有更佳的杀伤肿瘤细胞的作用和很低的毒副作用。数据采用方差齐性检验 ,Fu注射剂瘤体注射组、Fu聚乳酸微球瘤体内注射低剂量组、Fu聚乳酸微球瘤体内注射高剂量组与无药聚乳酸微球组比较 ,瘤重消减 (P <0 0 0 5 )有显著性差异 ,且微球内FU浓度越高 ,疗效越好。而Fu注射剂腹腔注射组与此组比较 (P >0 0 5 ) ,无统计学意义。结论Objective: By means of animal experiment to make a feasibility trial for establishing the concept of “implanting and targeting continuous interstitial chemotherapy'(ITCIC),and to compare the efficacy of this new method of chemotherapy with other chemotherapeutic methods.Methods:The biocompatible and biodegradable poly-lactid was used as a sustained-releasing carrier and the microspheres that can sustained-release Fu(flurouracil)were prepared to be used for the continuous interstitial chemotherapy by means of implanting and passive targeting method,i.e.Fu poly-lactid microspheres were injected directly into the transplanted tumour mass or into the adjacent peri-tumor tissue from a local high Fu dose area,depending upon the osmosis mechanism,Fu was steadily and continuously osmosed into the malignant tumor cells to kill them.The experimental mice were randomized into 6 groups,receiving different treatments (detailed in the text) for making comparison. The efficacy,toxicity and side-effect of the Fu-poly-lactid microsphere ITCIC method were evaluated quantitatively by pathological study of the section slides,and statistics was made with standard methods,and also the comparison of these results with those of other chemotherapeutic methods was made.Results:Fu poly-lactid microspheres demonstrated an ideal curve of stably sustained-releasing Fu without the bursting effect.Our results showed that the Fu-poly-lactid microsphere ITCIC method group demonstrated the best treatment results with the least toxicity and side-effects in comparision with those of other groups,(P<0.005),and the higher the concentration of Fu in the microspheres,the better treatment results would be,but there was no statistic difference observed between the intra-peritoneal cavity injection of Fu group and the no-drug group.Conclusion:According to our results of the feasibility trial of animal experiment,we consider that the concept of ITCIC can be established and this method of chemotherapy may probably to obtain the best treatment results for e

关 键 词：植入靶向持续组织间化疗 可行性 动物实验 聚乳酸 缓释药物载体 氟脲嘧啶 

分 类 号：R73-36[医药卫生—肿瘤]