甘草次酸修饰海藻酸钠纳米给药系统的肝靶向性评估  

QUALITATIVE AND QUANTITATIVE EVALUATION OF GLYCYRRHETINIC ACID MODIFIED ALGINATE LIVER TARGETING DRUG DELIVERY SYSTEMS

作　　者：张闯年[1] 王平[1] 赖全勇[1] 张倩[1] 张玥[1] 吴玉昆[1] 刘通[2] 王蔚[1] 袁直[1] 

机构地区：[1]南开大学高分子化学研究所功能高分子材料教育部重点实验室,天津300071 [2]苏州大学材料与化学化工学部,苏州215123

出　　处：《高分子学报》2011年第8期817-823,共7页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号50873048;51073080);天津科技支撑计划(项目号10ZCKFSY07500)资助项目

摘　　要：通过EDC/NHS偶联反应将疏水性肝靶向小分子甘草次酸(GA)连接到天然多糖海藻酸钠(ALG)上,制备了具有双亲性肝靶向药物载体材料(GA-ALG).采用乳化法对广谱抗癌药物阿霉素(DOX)进行包载,得到肝靶向载药纳米粒子(DOX/GA-ALG NPs).利用单光子发射型计算机断层成像技术(SPECT)和药物体内分布实验对DOX/GA-ALG NPs的肝靶向性进行了评估.SPECT成像显示,99mTc标记空白纳米粒子(99mTc-GA-ALG NPs)主要集中在Wistar大鼠的肝脏部位,富集率达40.2%.药物体内组织分布结果显示,尾静脉注射3 h后,DOX/GA-ALG NPs组小鼠肝脏中阿霉素浓度达到67.7μg/g,是DOX.HCl组的4.7倍.相对摄取率(re)、靶向效率(te)和加权平均靶向效率(te*)数据同样表明DOX/GA-ALG NPs具有显著肝靶向能力.研究表明甘草次酸修饰海藻酸钠纳米给药系统具有良好的肝靶向性.Glycyrrhetinic acid modified alginate（GA-ALG） was prepared by covalent attachment of hydrophobic liver targeting ligand glycyrrhetinic acid（GA） onto the nature polysaccharide alginate（ALG）.The resulting amphiphilic GA-ALG could form self-assembled nanoparticles（GA-ALG NPs） in an aqueous medium as liver targeting drug delivery carrier.Broad spectrum antitumor drug-doxorubicin（DOX） loaded GA-ALG NPs（DOX/GA-ALG NPs） were obtained by emulsification method for liver targeting drug delivery.Single photon emission computed tomography（SPECT） and some mathematical relationships were used to qualitatively and quantitatively evaluate the targeting efficiency of GA-ALG drug delivery systems in vivo.The SPECT image confirmed that 99mTc labeled GA-ALG nanoparticles mainly accumulated in the liver of Wistar rats after intravenous injection,and the accumulation of 99mTc labeled GA-ALG nanoparticles in the liver was about 40.2% at 3 h after injection.The biodistribution data showed that the concentration of DOX in the liver reached（67.8 ± 4.9） μg/g after intravenous administration of DOX/GA-ALG NPs,which was 4.7-fold higher than that of DOX·HCl solution at 3 h post-injection.And the data of relative tissue exposure（re）,targeting efficiency（te） and weighted-average targeting efficiency（t＊e） showed that liver targeting efficiency was enhanced by GA-ALG drug delivery systems.These results revealed the potential of GA-ALG nanoparticles as liver targeting drug delivery carriers.

关 键 词：甘草次酸 海藻酸盐 纳米给药系统 靶向效率 

分 类 号：TQ463[化学工程—制药化工]