表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒在大鼠肝脏组织中的靶向研究

Study of the targetting distribution of epirubicin polybutylcyanoacrylate magnetic nanoparticles in rat hepatic

目的 制备表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒（EPI-PBCA-MNPS）并进行表征,进一步分析该药在大鼠肝脏分布情况,研究其靶向性。方法 在EPI-PBCA-NPS研究的基础上,采用微乳液反相界面聚合法制得表阿霉素聚氰基丙烯酸正丁酯磁性纳米粒（EPI-PBCA-MNPS）,然后表征;将SD雄性大鼠随机分为3组：A组为EPI组（表阿霉素组）、B组为EPI-PBCA-MNPS组;C组为EPI-PBCA-MNPS＋磁场组,并分为两个亚组,实验中测定血浆中表阿霉素浓度即C非靶区肝组和测定肝脏内肝组织中表阿霉素浓度即C靶区肝组。每组15只,分别通过尾部静脉注射,观察各组靶向分布情况。采用SPSS 13.0统计软件进行数据统计处理,计量资料以x珋±s表示,采用t检验;计数资料采用χ^2检验。以P〈0.05为差异有统计学意义。所有数据均进行方差齐性检验及符合正态分布。检验水准a=0.05。结果 EPI-PBCA-MNPS粒径为（151.3±29.6）nm,分布均匀,胶体溶液长期稳定,平均包封率为（80.26±14.22）%,平均载药量为（14.64±2.13）%,饱和磁化强度为：0.34 KA/m;尾部静脉给药后,肝脏组织中表阿霉素浓度较高,其药物最高浓度提前至5 min,并明显减少了在脾中的分布情况,进一步使肝脏组织中的分布显著提高。在磁场环境中,C靶区肝组中表阿霉素浓度显著升高,并明显高于C非靶区肝、A组及B组（P〈0.05）。结论 EPI-PBCA-MNPS具有较好的磁感应性,大鼠静脉注射并在磁场环境中能够显著提高表阿霉素在靶肝区聚集的程度,并进一步降低表阿霉素在其他非靶肝区聚集的程度。

Objective To prepare and characterize epirubicin polybutylcyanoacrylate magnetic nanoparticles （EPI-PBCA-MNPS） , and to offer a new dosage form of high-performance for targeted therapy of hepatoma, with further analyzing the distribution of the drug in rat liver. Methods Based on EPI-PB- CA-NPS research foundation, EPI-PBCA-MNPS was prepared by a reversed-phase micro-emulsion polymerization method, of which reactive condition was correlatively characterized. The SD male rats were randomly divided into three groups ： EPI （A） group ; EPI-PBCA-MNPS （ B ） group ; the external magnetic field （ C ） group, and is further divided into two sub-groups. The determination of plasma concentration of epirubicin： Cnon-targeted liver group and determination of liver tissue concentration of epirubicin ： Ctargeted liver group through the tail vein injection with 15 rats in each group. The targeted distribution was analyzed. P 〈 0.05 was thought to be statistically significant. Results EPI-PBCA-MNPS was uniformly and stably distributed in the colloid solution with the mean particle diameter of 151.3 ± 29.6 nm. The mean envelopment rate, drug-loading, saturated magnetization intensity is 80. 26 ± 14. 22%, 14. 64 ± 2. 13%, 0. 34 KA/m, respectively. After Tail vein injection, EPI concentration was significantly increased in the liver. The peak ahead of the drug was about 5min, with significantly reduced the EPI distribution in the spleen. The aggregation degree of liver was significantly enhanced. The accumulation of epirubiein in Ctargeted liver group was significantly higher by using an external magnetic field when compared to the Cnon-targeted liver group, A group and B group （ P 〈 0.05 ）. Conclusion EPt-PBCA-MNPS had good magnetic response. An extraorgan magnetic field can significantly increase the accumulation of pharmonabicin in target liver, reducing the accumulation in other non-target organs.