摘要
目的研究苦参素固体脂质体纳米粒(SLN)的动物体内行为,探讨苦参素SLN作为肝靶向给药系统的可行性。方法采用“乳化蒸发-低温凝固”法制备苦参素SLN,平均粒径104nm,表面电位-32.6mV,包封率为81.0%。将苦参素SLN悬液与苦参素水溶液分别大鼠尾静脉注射100mg·kg-1,于不同时间尾静脉取血,测定血中苦参素浓度,提取药动学参数。将苦参素SLN悬液与苦参素水溶液小鼠尾静脉注射100mg·kg-1,于不同时间取血、心、肝、脾、肺、肾,测定各组织中药物浓度,计算靶向指数、靶向效率及相对靶向效率等参数。结果大鼠尾静脉注射苦参素水溶液和苦参素SLN悬液100mg·kg-1后,药动学结果显示,体内过程符合二室开放模型,与苦参素水溶液相比,苦参素SLN的t1/2β延长5.5倍,AUC增加了3.9倍。小鼠尾静脉注射苦参素水溶液和苦参素SLN悬液100mg·kg-1后,体内分布结果显示:苦参素SLN给药后在肝和血中的分布较水溶液有明显提高,30min时药物在肝中的浓度是水溶液的12倍,相对靶向效率为360%。结论SLN明显改变了苦参素的药动学行为,使消除变慢,生物利用度增加。苦参素SLN具有明显趋肝性,可靶向于肝,延长药物在血和肝中的滞留时间。
Abstract
OBJECTIVE To study the pharmacokinetics and tissue distribution of oxymatrine-SLN in animal and investigate the liver targeting effect of oxymatrine-SLN. METHODS Oxymatrine-SLN composed of oxymatrine, phospholipid and stearic acid were prepared by “emulsion- evaporation- solidified at low temperature” process. The average diameter of the particles was 104 nm, Zeta potential was -32.6 mV, and encapsulation efficiency was 81.0%. The pharmacokinetics of rats after intravenous administration of oxymatrine-SLN and oxymatrine solution 100 mg·kg-1 was studied and the concentrations of oxymatrine in plasma, liver, lung, heart, spleen and kidney of mice were determined after intravenous administration 100 mg·kg-1 in mice.RESULTS The plasma concentration-time curves were discribed by a two-compartment model. The t1/2β of oxymatrine-SLN group was 5.5 times longer than oxymatrine solution group and the AUC of oxymatrine-SLN group was increased by 3.9 times compared with oxymatrine solution group. The tissue distribution of oxymatrine-SLN was different from that of free oxymatrine. The mean content of oxymatrine in liver at 30 min of oxymatrine-SLN group was 12 times greater than that of the oxymatrine solution group. Compared with oxymatrine solution, the relatively target efficiency to liver tissue was 360%.CONCLUSION It is demonstrated that oxymatrine-SLN has selective targeting to liver tissue and the liver targeted oxymatrine-SLN seem to have significant advantages and good development value.
关键词
苦参素 /
固体脂质纳米粒 /
药动学 /
体内分布
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Key words
oxymatrine /
solid lipid nanoparticles /
pharmacokinetics /
drug distribution /
liver target
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孙洁胤;周芝芳;刘放;陈国神.
苦参素固体脂质纳米粒的药动学和体内分布[J]. 中国药学杂志, 2007, 42(14): 1091-1094
SUN Jie-yin;ZHOU Zhi-fng;LIU Fng;CHEN Guo-shen.
Pharmacokinetics and Tissue Distribution of Oxymatrine-SLN [J]. Chinese Pharmaceutical Journal, 2007, 42(14): 1091-1094
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参考文献
[1] WANG Y,MWNG-GEN D L,ZHEN W Y,et al. Pharmacokinetics of oxymatrine injection healthy volunteers[J] . Chin J Clin Pharmacol(中国临床药理学杂志),2003,19(4):301-302,305.
[2] YU B T,SUN X,ZHANG Z R. Enhanced liver targeting by synthesis N1-steary- 5-Fu and incorporation into solid lipid nanoparticles[J] . Arch Pharm Res,2003,26(12): 1096-1101.
[3] CHENG J H,WANG Z M,WU D C,et al. Body distribution of nanoparticles-associated adriamycin after administration into the hepatic artery of hepatoma-bearing rats[J] . Acta Pharm Sin(药学学报),1999,33(3):164-167.
[4] ZHANG L,XIANG D,HONG Z,et al. Studies on the liver targeting of norcantharindin microemulsion[J] . Acta Pharm Sin(药学学报),2004,39(8):650-655.
[5] PENG Y X,ZHUANG Y L,LIAO G T. Study on bone marrow targeting daunorubicin polybutylcyanoarylate nanoparticles[J] . Chin J Pharm(中国医药工业杂志),2000,31(2):57-61.
[6] MENG-GEN D L,WANG Y,JIA F Q. Reversed phase ion-pair HPLC determination of oxymatrine[J] . Chin J Pharm Anal(药物分析杂志),2003,23(6):440-443.
[7] XIE M Z,ZHOU W Z,ZHANG Y. The metabolism of oxymatrine[J] . Acta Pharm Sin(药学学报),1981,16(7):481-487.
[8] WANG M L,ZHOU Q L,WANG B X. Studies on metabolism of oxymatrine by human intestinal bacteria[J] . China J Chin Meter Med(中国中药杂志),2001,26(4):272-274.
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脚注
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基金
浙江省中医药管理局青年基金资助项目(2004Y012)
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