鳖甲肽脂质体药代动力学及肝靶向分析  

Pharmacokinetics and Hepatic Targeting of Trionycis Carapax Peptide Sterically Stabilized Liposomes

作　　者：汤晗霄 赵天文[1] 黄宇[1] 盛云杰[1] 郑杭生[1] 张永生[1] 

机构地区：[1]浙江中医药大学药学院,杭州310053

出　　处：《中国实验方剂学杂志》2017年第9期68-73,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81573700);浙江省自然科学基金项目(LY16H280004)

摘　　要：目的:制备含DiR碘化物荧光染料的长循环脂质体(DiR-SSL),采用SD大鼠和BALB/c裸鼠进行荧光成像的体内靶向性研究,利用空白SSL包封含5-羧基荧光素(5-FAM)的鳖甲肽(HGRFG-5-FAM,HF)制备HGRFG-5-FAM-SSL(HFL),研究HF及HFL分别给药于大鼠的药代动力学。方法:采用薄膜分散法制备DiR-SSL及HFL,取2组SD大鼠分别尾静脉注射HF及HFL,其HF质量浓度及剂量一致,于不同时间点采血,利用多功能微孔板检测仪分析HF血药浓度,计算药代动力学参数;将DiR-SSL尾静脉注射于BALB/c裸鼠,分别于1,2,5,7,24 h活体成像,读取荧光强度值;取正常SD大鼠尾静脉注射DiR-SSL,24 h后解剖心、肝、脾、肺、肾于荧光成像系统成像并读取荧光强度值,将肝组织冷冻切片进行激光共聚焦扫描。结果:HF注射到SD大鼠体内,其半衰期(T_(1/2))仅0.826 h,而HFL在相同剂量下,T1/2和药时曲线下面积(AUC_(0-∞))分别为HF的16.253,11.899倍;在BALB/c裸鼠活体成像中,荧光主要集中于肝脏位置,随着时间增加荧光强度逐渐减弱;SD大鼠各脏器中的DiR-SSL荧光在肝脏中最强,注射24 h后DiR-SSL仍能在肝脏储留。结论:SSL递药系统能显著延长HF在SD大鼠体内的T_(1/2)。SSL递药系统具有肝靶向作用,提示该系统可作为药物载体进行肝靶向递药。Objective： In this study,sterically stabilized liposomes （SSL） containing DiR-iodide fluorescent dye （DiR-SSL） was prepared,this liposome was performed on SD rats and BALB/c nude mice for in vivo targeting studies.HGRFG-5-FAM-SSL （HFL） was preparing by SSL loading Trionycis Carapax peptide containing 5-carboxylfluorescein（5-FAM） （HGRFG-5-FAM,HF）,and to investigate pharmacokinetics of administration by HF and HFL in rats,respectively. Method： DiR-SSL and HFL were prepared by thin-film dispersion method.HF and HFL were injected into the tail vein of two groups of SD rats,respectively;the concentration and dose of HF were the same.Plasma samples were collected at different time points and analyzed by multi-function microplate detector,and pharmacokinetic parameters were calculated.DiR-SSL was injected intravenously in BALB/c nude mice,the mice were in vivo imaged respectively at 1,2,5,7,24 h,and fluorescence values were read.The normal SD rats were injected DiR-SSL intravenously,after 24 h,the heart,liver,spleen,lung and kidney were imaged in fluorescence imaging system and fluorescence values were read,frozen sections of liver tissue were taken for confocal laser scanning. Result： After HF being injected into rats,its T1/2 was only 0.826 h;at the same dose,T1/2 and AUC0-∞ of HFL were 16.253 times and 11.899 times that of HF,respectively.In vivo fluorescence imaging of BALB/c nude mice showed fluorescence was mainly in the liver position and weakened gradually over time.The fluorescence of DiR-SSL in the liver of SD rats among different organs was strongest,DiR-SSL remained in the liver tissue at 24 h after injection. Conclusion： SSL drug delivery system can significantly extend T1/2 of HF in SD rats,and this system has a liver targeting effect,suggesting that this system can be used as drug carriers to realize liver targeted drug delivery.

关 键 词：肝靶向 长循环脂质体 DIR 鳖甲肽 药代动力学 5-羧基荧光素 

分 类 号：R969.1[医药卫生—药理学] R945[医药卫生—药学]