聚乳酸-替莫唑胺微胶囊对大鼠C6脑胶质瘤体外和体内抑瘤试验

Growth inhibition of polylactic acid temozolomide microspheres on SD rat C6 brain glioma in vitro and in vivo

目的观察聚乳酸-替莫唑胺(PLA-TMZ)微胶囊对大鼠C6脑胶质瘤体外和体内抑瘤效果。方法C6细胞悬液内分别加入不同浓度PLA-TMZ微胶囊样品、市售TMZ、TMZ原料药作MTT检验,对比其体外抑瘤率。将C6细胞悬液注入SD大鼠腋部皮下和皮层S1区构建皮下和脑内胶质瘤模型,在肿瘤间质内注射PLA-TMZ微胶囊和TMZ原料药,观察对比肿瘤体积变化和SD大鼠生存期。结果大鼠C6脑胶质瘤细胞抑制率达到50%时的药物浓度(IC50):微胶囊样品200μg/ml;市售TMZ400μg/ml;TMZ原料药未达到50%抑制率。PLA-TMZ微胶囊在皮下和脑内均有显著抑瘤作用(P<0.01),并能延长脑内胶质瘤模型大鼠的生存期(中位生存期42dvs.31d,P<0.01)。结论PLA-TMZ微胶囊剂可做为瘤内注射治疗胶质瘤的有效制剂。

Objective To investigate the anti-tumor effect of polylactic acid temozolomide （PLA-TMZ） microsphere on SD rat C6 brain glioma in vitro and in vivo.Methods The anti-tumor effects in vitro were researched by adding different concentration of self-produced PLA-TMZ microspheres,commercialized TMZ and TMZ raw material medicine into C6 cell suspension.The tumor inhibitin rate was repectively evaluated via MTT assay.C6 cell suspension was inoculated subcutaneously to the axilla and S1 cortex of SD rats to make glioma models. The tumor volume and survival period of the rats were compared among the groups of self-produced microspheres,raw material medicine and the control by interstitial injection. Results The concentration of testing drug for 50% tumor inhibition（IC50） on rat C6 brain glioma in vitro was 200μg/ml for self-produced microspheres and 400μg/ml for commercialized TMZ. IC50 of raw material medicine was not reached in the experiment. The anti-tumor effects of self-prduced microspheres on glioma model of the axilla and S1 cortex of SD rats were significant （P〈0.01）. And survival period of the rats with glioma models in S1 cortex was extended significantly with average survival of 42 days,which was longer than 31 days in control group （P〈0.01）. Conclusion PLA-TMZ microsphere is effective to treat brain glioma by interstitial injection.