摘要目的 观察自制阿霉素-N-琥珀酰壳聚糖纳米缓释微粒在体内、外释药效果及对小鼠C6胶质瘤动物模型的治疗作用.方法 合成阿霉素-N-琥珀酰壳聚糖纳米缓释微粒,检测其在人工脑脊液及20只正常SD大鼠脑内药物释放的情况.检测阿霉素-N-琥珀酰壳聚糖纳米缓释微粒对20只脑内荷瘤SD小鼠生存期的影响以及对20只SD小鼠皮下接种肿瘤生长的抑制作用.结果 阿霉素-N-琥珀酰壳聚糖纳米缓释微粒在人工脑脊液和兔脑内可持续释放达30 d以上;局部控释化疗可明显延长脑内荷瘤小鼠的生存期,实验组中位生存时间为35 d.局部阿霉素控释化疗对于皮下肿瘤有明显抑制效应,与注射的对照组比较,实验组小鼠皮下瘤体生长减慢甚至停止生长,两组之间肿瘤体积差异有统计学意义(x2=7.68,P＜0.05),肿瘤细胞凋亡指数为:对照组为6.4％、实验组为59.3％,差异有统计学意义(x2=23.59,P＜0.05).结论 阿霉素-N-琥珀酰壳聚糖纳米缓释微粒的控释化疗在避免系统化疗全身毒性的同时,增加肿瘤局部药物浓度,可有效抑制肿瘤生长.

abstractsObjective To observe the in vitro and in vivoreleasing effects of adriamycin-N-succinyl chitosan (SCS) sustained release nanometer particles following implantation,and evaluate the local chemotherapeutic effect on rats bearing C6 gliomas.Methods The matrix with adriamycin was prepared.Gelatin and agar were used as major materials.The releasing effects of adriamycin-SCS sustained release nanometer particles were determined in artificial cerebrospinal fluid or in 20 normal rats brains by the method of fluorometry.The median survival time (MST) was measured in 20 SD rats bearing intracranial C6 gliomas,and the inhibitory effect of regional administration of adriamycin-SCS on growth of subcutaneous tumors was evaluated in 20 rats.Results Constant-release of adriamycin-SCS lasted over 30 days in artificial cerebro-spinal fluid or normal rabbit brains.Local controlled release of adriamycin could prolong the survival of rats bearing C6 gliomas with the MST being 35 days.Local controlled release of adriamycin could significant inhibit the growth of the subcutaneous tumors.As compared with control group,the growth of the subcutaneous tumors was slowed down or ceased in experimental group.There was statistically significant difference in tumor volume between the two groups (x2 =7.68,P ＜ 0.05).There was significant difference in apoptosis index between control group (6.4％) and experimental group (59.3％,x2 =23.59,P ＜ 0.05).Conclusion With high regional concentration and avoidance of toxicity of systemic chemotherapy,control released chemotherapy of adriamycin-SCS sustained nanometer particles remarkably inhibited the growth of C6 gliomas.