生物降解性阿霉素聚乳酸微球体外释放及对视网膜毒性的研究  

In-vitro release and retinal toxicity of biodegradable polylactic acid microspheres containing adriamycin

作　　者：刘瑜玲[1] 陈改清[2] 荆文涛[3] 张强[4] 何蕾[4] 徐亮[5] 张士元[6] 

机构地区：[1]北京医科大学第三医院眼科,100083 [2]首都医科大学化学教研室 [3]中国长城公司总医院眼科 [4]北京医科大学药学院 [5]北京市眼科研究所 [6]北京市眼科研究所4

出　　处：《中国实用眼科杂志》2001年第1期34-36,共3页Chinese Journal of Practical Ophthalmology

基　　金：北京市教委科技发展基金

摘　　要：研究生物降解性阿霉素聚乳酸微球的体外释放及其对视网膜的毒性。方法 :采用溶媒挥发法制备生物降解性阿霉素聚乳酸微球。用扫描电镜观察其形态 ,荧光分光光度法观测其体外释放情况 ;2 8只兔用于间接检眼镜、ERG、光镜和透射电镜检查以评价药物的视网膜毒性。结果 :制得的微球平均粒径为 37.9μm,其中阿霉素载药量为 2 .85 % ;体外释放速率缓慢 ,第 42天时阿霉素的释放率仅达 6 6 .44% ;观察表明 ,游离阿霉素剂量超过 5 μg或阿霉素聚乳酸微球超过 1 5 μg时 ,视网膜出现毒性反应。结论 :阿霉素聚乳酸微球较游离阿霉素毒性小 ,具有缓释长效的特点 ,提示该制剂有可能成为一种有效的治疗增生性玻璃体视网膜病变的眼内释药系统。To study the in-vitro release and retinal toxicity of a new intraocular drug delivery system,the biodegradable polylactic acid microspheres containing adriamycin(ADR-PLA-MS)for treatment of proliferative vitreoretinopathy(PVR).Method:The ADR-PLA-MS was prepared by solvent-evaporation technique.The morphology of ADR-PLA-MS was examined by transmission electron microscope,while the release of adriamycin from ADR-PLA-MS was monitored by a fluorospectrophotometer.Twenty-eight pigmented rabbits were randomly divided into three groups.Rabbits in group 1 and 2 received intravitreal injection of the ADR and ADR-PLA-MA at different doses respectively.Rabbits in group 3 were taken as control and received intravitreal injection of saline solution.After intravitreal injection,the eyes were examined by ophthalmoscopy,slit-lamp microscope,transmission electrone microscope,and ERG.Results:4 weeks later,toxicity to retina was observed when the dose of ADR was over 5μg or the dose of ADR-PLA-MA over 15μg.Conclusions:The results suggest that ADR-PLA-MA reduce the toxicity of ADR to retina and may be potential drug delivery system in the treatment of PVR.

关 键 词：生物降解性微球 聚乳酸 阿霉素 体外释药 视网膜毒性 

分 类 号：R774.1[医药卫生—眼科] R944.9[医药卫生—临床医学]