脑靶向脂质体配体维生素C-胆甾偶联物的设计合成及初步脑靶向评价  

Design,synthesis and preliminary evaluation of vitamin C-cholesterol as ligand for brain targeting liposomes

作　　者：陈洋 赵毅[2] 吴勇[2] 马超英[1] 张涛[3] CHEN Yang;ZHAO Yi;WU Yong;MA Chao-ying;ZHANG Tao(College of Medicine, Southwest Jiaotong University, Chengdu 610031, China;West China School of Pharmacy, Sichuan University, Chengdu 610041, China;Oncology Center of General Hospital of Chengdu Military District, Chengdu 610083, China)

机构地区：[1]西南交通大学医学院,四川成都610031 [2]四川大学华西药学院,四川成都610041 [3]成都军区总医院肿瘤中心,四川成都610083

出　　处：《中国药物化学杂志》2018年第3期195-198,224,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金面上项目(81573286;81773577)

摘　　要：目的合成一种新型的脑靶向脂质体配体——维生素C-胆甾偶联物,并初步评价其脑靶向性。方法以胆固醇和维生素C为原料,经9步反应得到目标配体。利用薄膜分散法制备脑靶向多西紫杉醇脂质体,通过HPLC法测定给药后小鼠脑中的药物浓度。结果与结论制备得到的配体经1H-NMR和MS谱确证。体内分布实验显示,该配体修饰的脂质体,其脑内多西紫杉醇的摄取率和峰浓度比分别是游离药物的2.51和4.38倍。本研究所设计并制备的维生素C-胆甾修饰脂质体是一种高效的脑靶向给药系统。In this study, a novel brain targeting vitamin C （Vc ） derivative was designed and synthesized as liposome ligand for preparing novel liposome to achieve the effective delivery of drug formulations to brain by glucose transporter 1 （ GLUT1 ） and the Na^＋ -dependent vitamin C transporter （ SVCT2 ）. The liposome was prepared and characterized for particle size, Zeta potential and encapsulation efficiency. The preliminary evaluation in vivo demonstrated that ligand Vc-cholcoated liposome had an improved targeting ability and significantly increased the area under the concentration-time of docetaxel （DTX） in brain compared to naked docetaxel and non-coated liposome. The relative uptaking efficiency and concentration efficiency were enhanced by 2.51- and 4.38-fold compared to that of naked docetaxel, respectively. Both distribution data and pharmacokinetic parameters suggested that the Vc-Chol-modified liposomal delivery system was a promising carder to enhance CNS drug＇s delivery ability into brain.

关 键 词：脑靶向 脂质体配体 维生素C-胆甾偶联物 合成 给药系统 

分 类 号：R914[医药卫生—药物化学]