论文部分内容阅读
目的研究局部重复应用聚乳酸[poly(D,L-lactic acid),PLA]控释卡莫司汀[1,3-bis(2-chlorethyl)-1-nitrosourea,BCNU]微球(BCNU-PLA)对U251人脑胶质瘤的生长抑制作用。方法应用沉淀方法制备包载BCNU的PLA纳米微球。应用扫描电子显微镜观察载药微球形态,分别应用Bratton-Marshall比色法和紫外分光光度法测定微球载药率与药物释放曲线。应用MTT方法检测PBS、BCNU、PLA微球和BCNU-PLA等不同处理方法对U251胶质瘤细胞增殖活性的影响。应用U251裸鼠皮下移植瘤模型为研究对象,连续3次进行PBS、BCNU、PLA微球和BCNU-PLA的治疗,观察实验动物的生存期与皮下肿瘤生长情况。结果扫描电子显微镜观察载药纳米微球呈球形,具有良好的单分散性;BCNU-PLA平均粒径为23.5μm。BCNU-PLA平均载药率为11.5%;以相对分子质量30×103的PLA制备BCNU-PLA微球的体外药物释放分析显示:BCNU在释放开始的10d表现出较大的突释,释放量达到载药量的40%;随后进入控释期,至4周左右释放了所载药物的50%。与BCNU原药治疗组比较,BCNU-PLA控释微球治疗在体外持续抑制U251胶质瘤细胞的生长;在体内明显抑制裸鼠皮下荷U251胶质瘤的生长,并显著改善荷瘤鼠的全身状况。结论BCNU-PLA载药微球可有效抑制皮下荷U251胶质瘤的生长,是局部化疗治疗胶质瘤的一种新策略。
OBJECTIVE: To investigate the effect of locally administered BCNU-PLA (poly-D, L-lactic acid) ) On the growth inhibition of U251 human glioma. Methods Precipitation method was used to prepare BCNU-loaded PLA nanospheres. The microspheres morphology was observed by scanning electron microscopy. The drug loading rate and release curve of microspheres were measured by Bratton-Marshall colorimetry and UV spectrophotometry respectively. The effects of PBS, BCNU, PLA microspheres and BCNU-PLA on the proliferation of U251 glioma cells were detected by MTT assay. U251 subcutaneously transplanted tumor model in nude mice was used as the research object. The PBS, BCNU, PLA microspheres and BCNU-PLA were treated three times in a row, and the survival and subcutaneous tumor growth of the experimental animals were observed. Results Scanning electron microscopy showed that the drug-loaded nanospheres were spherical and had good monodispersity. The average diameter of BCNU-PLA was 23.5μm. BCNU-PLA average drug loading rate of 11.5%; BCNU-PLA microspheres prepared with PLA of relative molecular mass of 30 × 103 in vitro drug release analysis showed that: BCNU in the beginning of the release of 10d showed a larger burst release, release reached 40% of the drug load; then into the controlled release period, to about 4 weeks released 50% of the drug contained. BCNU-PLA controlled release microspheres treatment continued to inhibit the growth of U251 glioma cells in vitro and significantly inhibited the growth of U251 glioma in nude mice in vivo, and significantly improved the tumor-bearing mice General condition Conclusion BCNU-PLA drug-loaded microspheres can effectively inhibit the growth of U251 glioma, which is a new strategy of local chemotherapy for glioma.