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期 刊 ：中国中药杂志 2005年 30卷 11期 页码：817.

关键词：土贝母；肝癌；靶向给药系统；纳米粒；

Keywords:Bolbstemma paniadatum, liver cancer, targeted drug delivery systems, nanoparticles, toxic and side effects,

摘 要 ：目的:研制中药土贝母抗癌有效成分TBMS的肝靶向给药系统,并考察该给药系统的减毒作用。方法:以α-氰基丙烯酸正丁酯为载体材料,用系统全面反馈动态技术优化纳米粒制备工艺,并进行其制剂学性质及毒理学研究,用透射电镜观察纳米粒的小鼠体内靶向性、XXTX-2000组织病理图象数据自动定量分析管理系统观察其减毒作用。结果:制得D₅₀为0.68μm、大小较均匀的纳米粒,载药量、包封率分别为(37.33±0.19)%,(88.63±0.13)%。体外释放符合Weibull方程,释放达平衡时间与t_1/2分别较注射剂延长26倍和19倍。纳米粒结构主要分布在肝脏组织中,且纳米粒对肺和肝脏的毒性明显较注射剂低。纳米粒的LD₅₀高于注射剂13.5%,同时血管刺激性较TBMS注射剂大大降低。结论:采用肝靶向给药系统的手段,可使土贝母抗癌有效成分TBMS达到肝靶向的目的,同时有望解决阻碍应用于临床的毒性问题,为土贝母抗癌有效成分的进一步研究开发奠定了基础。

Abstract:Objective: To study the liver targeted drug delivery system of TOMS——the effective anticancer component from Bolbstemma paniculatum, and to discuss the system‘s function of decreasing toxicity. Method: BCA was used as carrier material. The preparation technology of nanoparticles was optimized through overall feedback dynamic techniques. The properties of preparation and toxicology were also studied. Thenanoparticles‘ targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. Result: D₅₀ was 0.68 μm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t_1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles‘ LD₅₀ exceeded injection‘s by 13.5% and their stimulus was much lower than injection. Conclusion:The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

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