立体定向注射靶向性缓释BCNU聚乳酸微球治疗C6胶质瘤的研究  被引量:6

Growth inhibition against intracranial C6 gliomas by stereotactic delivery of BCNU from controlled release of poly (D,L-lactic acid) microspheres

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作  者:康春生[1] 原续波[1] 浦佩玉[2] 郭艳霜[1] 巴达尼[2] 李彦和[2] 王广秀[2] 谭健[3] 张富海[3] 常津[1] 盛京[1] 

机构地区:[1]天津大学材料科学与工程学院,300072 [2]天津医科大学总医院神经外科 [3]天津医科大学总医院核医学室

出  处:《中华神经外科杂志》2007年第2期103-106,共4页Chinese Journal of Neurosurgery

基  金:国家自然科学基金资助项目(50103008),天津市社会发展计划项目(023111511-2)

摘  要:目的 研究立体定向局部投递以转铁蛋白受体为配基的聚乳酸缓释卡莫司汀(BCNU)[Tf-(BCNU.PLA)]微球对C6胶质瘤的治疗效果。方法 以转铁蛋白为外水相,应用沉淀技术制备了表面含转铁蛋白、包载卡莫司汀的聚乳酸微球。分别应用Bratton-Marshall比色法与紫外分光光度法测定微球载药率与释放曲线。^99mTc标记微球后SPECT考察载药微球的体内分布,并进一步观察立体定向注射聚乳酸缓释BCNU微球后对C6胶质瘤的治疗效果。结果 载药微球呈球形,具有良好的单分散性;Tf-(BCNU-PLA)平均粒径为183.6nm。平均载药率为4.86%w/w;BCNU体外药物释放分析显示BCNU在释放开始的12h表现出较大的突释,释放量达到载药量的40%,随后进入缓释期,至180h释放了所载药物的60%。立体定向注射2h后Tf-PLANPs仍滞留于原位,胸腔和腹腔器官均未显示放射性活性。14h后放射活性减至接近本底,Tf-PLANPs仍在注射位点保持了良好的滞留性。与对照组相比,注射Tf-(BCNU-PLA)的大鼠生存期显著延长,核磁共振图像显示其中2只大鼠颅内肿瘤消失。结论 Tf-(BCNU-PLA)微球可有效延长荷瘤大鼠的生存时间,对恶性脑胶质瘤具有抑制作用。Objective To study the inhibitory effects of stereotactic delivery of BCNU-releasing from poly (lactic acid) microspheres coated with transferring [ Tf-(BCNU-PLA) ] against C6 gliomas, Methods Tf-( BCNU PLA) was prepared through nano precipitation technology using transferrin solution as external aqueous phase. Bratton Marshall colorimetric method and spectrophotometry were used respectively to determine the drug loading and release behavior. The biodistribution of microspheres labeled by 99mTc after stereotactic delivery into rat brain bearing C6 glioma was studied via SPECT, the therapeutic effect of Tf- (BCNU)-PLA was further studied by the rat C6 glioma model. Results The resulting particles were fractured and showed the characteristic alveolar morphology. The average particle size was 183.6nm for Tf- (BCNU-PLA). The drug loading was 4.86% w/w. Drug release behavior in vitro indicated the burst effect was high (40%) after incubation for 12h, sustained drug release for 180h had been achieved. The radioactivity by SPECT could be detected only in rat brain 2 hours after injected the microspheres stereotactically, no radioactive foci outside the brain, such as hepatic region and heart. The radioactivities detected by SPECT indicated the Tf-(BCNU-PLA) was still retained in the delivery site until 14h after stereotactic injection. The growth inhibition against C6 gliomas in vivo was investigated by MRI, the prolongation of survival time is remarkable, and the C6 glioma in 2 rats model was eliminated in 60d. Conclusion The BCNU loaded poly(lactic acid) nanoparticles that coated with transferrin can prolong the survival time of C6 beating rats, thus have a good growth inhibition effect on C6 glioma.

关 键 词:神经胶质瘤 卡莫司汀 大鼠 立体定位技术 微球 

分 类 号:R686[医药卫生—骨科学]

 

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