长春碱纳米粒的细胞毒性和急性毒性研究

Cytotoxicity and acute toxicity study on vinblastine (VLB) nanoparticles

【目的】探讨长春碱聚氰基丙烯酸正丁酯纳米粒（VLB-PBCA-NP）对正常细胞的毒性及其急性毒性。【方法】采用MTT法并结合形态学观察,比较了VLB-PBCA-NP和VLB原料药对原代大鼠星形胶质细胞和小鼠成纤维细胞L929的毒性;用相同剂量的VLB-PBCA-NP和VLB原料药溶液对小鼠进行尾静脉注射,每日观察小鼠死亡情况,并计算半数致死量（LD50）。【结果】在质量浓度为0.5～50 ng/mL时,VLB-PBCA-NP和VLB原料药对星形胶质细胞增殖抑制率的影响无显著性差异,当质量浓度达到500和5000 ng/mL时,VLB-PBCA-NP对大鼠星形胶质细胞的毒性显著低于VLB原料药（P〈0.05）。5000 ng/mL的VLB-PBCA-NP对小鼠成纤维细胞L929的毒性为3级,极显著降低了VLB原料药的毒性（P〈0.01）。VLB-PBCA-NP和VLB原料药的LD50分别为26.38和22.7mg/kg,前者较后者提高了16.21%。【结论】VLB-PBCA-NP对小鼠的急性毒性和对非肿瘤细胞的毒性均显著低于VLB原料药。

[Objective] The aim of this study was to investigate toxicity of VLB poly（butyl cyanoacrylate） nanoparticles （PBCA-NP）. [Method] Difference between VLB-PBCA-NP and crude VLB on the growth of L929 and rat astrocyte was measured by MTT assay and morphology method. In addition,after the same dose of VLB-PBCA-NP and crude VLB solution were injected into mice tail vein,50% lethal dose of （LDs0） was counted. [Results] The results indicated that there was no significant difference on the effect of rat astrocyte growth between 0. 5 - 50 ng/mL VLB-PBCA-NP and crude VLB solution, but 500 and 5 000 ng/mL VLB-PBCA-NP significantly degraded cytotoxicity （P〈0.05）. 5 000 ng/mL VLB-PBCA-NP belonged to toxicity grade 3 on L929 fibroblasts growth,and very significantly degraded crude VLB toxicity. The LD50 of VLB-PBCA-NP and crude VLB solution was respectively 26.38 and 22.7 mg/kg. The LDs0 of VLB-PBCA-NP increased by 16.21% compared with crude VLB solution. [Conclusion] VLB-PBCA-NP degraded acute toxicity and nontumorous cells toxicity of crude VLB.