磁性阿霉素聚氰基丙烯酸正丁酯纳米粒的制备及药代动力学分析  

Preparation and Pharmacokinetics Study of Magnetic Doxorubicin Polybutylcyanoacrylate Nanoparticles

作　　者：周伟[1] 蔡林[1] 胡昊[1] 平安松[1] 王栋锋[1] 胡治平[1] 王冶[1] 

机构地区：[1]武汉大学中南医院骨科,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2009年第1期24-28,共5页Medical Journal of Wuhan University

基　　金：湖北省科技攻关计划基金资助项目(编号:2004AA304B08)

摘　　要：目的:通过磁性阿霉素聚氰基丙烯酸正丁酯纳米粒(ADM-PBCA-MNPS)的制备,研究ADM-PBCA-MNPS的理化性质并分析该微粒药代动力学特点。方法:乳化聚合法合成磁性阿霉素聚氰基丙烯酸正丁酯纳米粒,观察纳米粒的物理形态;检测纳米粒的饱和磁化强度和药物的包封率、载药量,通过体内外实验探讨磁性纳米微粒的释药性。结果:合成的磁性阿霉素聚氰基丙烯酸正丁酯纳米粒(ADM-PBCA-MNPS)平均直径194.30 nm;纳米粒的饱和磁化强度为0.488 emu/g,药物包封率为89.63%,载药量为9.73%;在体外条件下ADM-PBCA-MNPS显示出良好的缓释性能,体内药-时数据符合二室模型,ADM-PBCA-MNPS在大鼠体内的血药浓度-时间曲线下面积(AUC)、达峰浓度(Cmax)、消除半衰期(T1/2Beta)、平均滞留时间(MRT)均明显大于游离阿霉素(F-ADM)(P<0.01)。结论:制备的磁性纳米粒溶液性质稳定,符合在机体血管中随循环流动而不会沉淀的条件。实验组药物可在体内外缓慢释放阿霉素,有较高的生物利用度。Objective： To research on the physico-chemical property and nanoparticles pharmacokinetic characteristics of magnetic adriamycin polybutylcyanoacrylate nanoparticles （ADM-PBCAMNPS）. Methods： By emulsion polymerization, the physical form of nanoparticles was observed, the nanoparticles saturation magnetization and drug encapsulation efficiency was detected, and the drug release characteristics were researched in vitro and in vivo. Results： Average diameter of magnetic adriamycin polybutylcyanoacrylate nanoparticles （ADM-PBCA-MNPS） was 194.30 nm; nanoparticles saturation magnetization was 0. 488 emu/g, drug encapsulation efficiency reach 89. 63%, and the drug loading rate was 9.73%. ADM PBCA-MNPS showed good release properties in vitro, and also showed good properties at pharmacokinetics in the two-compartment model. The plasma concentration-time area under the curve （AUC）, peak concentration （Cmax）, the elimination half-life （T1/2 Beta）, mean residence time （MRT） of ADM-PBCA-MNPS in vivo were significantly greater than those of free doxorubicin （F-ADM） respectively （all P 〈 0. 01）.Conclusion： Prepared magnetic nanoparticles showed stable solution properties, which is capable for intravenous use in vivo, and the nanopartieles release doxorubicin slowly, which shows a fine bioavailability in vitro or in vivo.

关 键 词：磁性 阿霉素 聚氰基丙烯酸正丁酯 纳米粒 药代动力学 

分 类 号：R738[医药卫生—肿瘤]