基于紫杉醇前体药物构建白蛋白修饰脂质体及体内外抗肿瘤活性研究  

Preparation of Albumin Modified Liposomes Based on Paclitaxel Prodrug and Study on Their Antitumor Activity in Vitro and in Vivo

作　　者：葛建君[1,3] 李园园 车洪勇 陈放 李颢鑫 李凌冰 GE Jianjun;LI Yuanyuan;CHE Hongyong;CHEN Fang;LI Haoxin;LI Lingbing(Zaozhuang Vocational College of Science and Technology,Zaozhuang 277500,China;Yantai Food and Drug Inspection and Testing Center,Yantai 264035,China;Department of Pharmaceutics,School of Pharmaceutical Sciences,Cheeloo College of Medicine,Shandong University,Jinan 250012,China)

机构地区：[1]枣庄科技职业学院,山东枣庄277500 [2]烟台市食品药品检验检测中心,山东烟台264035 [3]山东大学齐鲁医学院药学院药剂教研室,济南250012

出　　处：《中国药学杂志》2025年第4期384-393,共10页Chinese Pharmaceutical Journal

基　　金：山东省重大科技创新工程项目资助(2018CXGC1411)。

摘　　要：目的 制备白蛋白修饰脂质体,通过与白蛋白受体的结合,实现对肿瘤组织的靶向转运。方法 合成紫杉醇-马来酰亚胺前体药物,并以此为基础构建前体药物脂质体。然后利用马来酰亚胺与白蛋白结构中游离巯基的自发结合制备白蛋白修饰脂质体,并对其体内抗瘤活性和靶向性进行验证。结果 通过肿瘤细胞表面白蛋白受体介导,荷载香豆素6的白蛋白修饰脂质体的细胞摄取量比游离香豆素6明显提高。体内抗肿瘤活性评价表明,制剂人血清白蛋白修饰紫杉醇前药脂质体(PTX@HSA-lipos)组具有比较好地控制肿瘤体积的效果。给药后生理盐水组平均瘤重为(7.88±1.22)g,而PTX@HSA-lipos为(3.126±0.68) g,瘤重数据变化具有显著差异(F=28.36,P<0.05)。结论 荷载紫衫醇的白蛋白修饰脂质体对肿瘤组织具有一定的靶向性,同时能够降低对正常细胞的影响。OBJECTIVE To prepare human serum albumin(HSA)modified liposomes,realize thetargeting ability bybinding to albumin receptor and achieve targeting transportto tumor tissues.METHODS The paclitaxel-maleimide prodrug was synthesized,and the prodrug loaded liposomes were constructed based on it.Then,albumin modified liposomes were prepared by spontaneous binding between maleimide and free mercapto group in albumin structure,and their pharmacological properties were characterized.Moreover,cell and animal experiments were conducted to further investigate the uptake ability of albumin modified liposomes by tumor cells,as well as its anti-tumor activity and targeting in vivo.RESULTS The cell uptake of albumin-modified liposomes mediated by overexpression of albumin-binding protein on tumor cell surface was significantly increased.The cell intake of coumarin-6 loaded albumin-modified liposomes was significantly higher than that of free coumarin-6.The evaluation of antitumor activity in vivo showed that the PTX@HSA-lipos group had a better effect on tumor volume control.After administration,the average tumor weight in the saline group was(7.88±1.22)g,and that in the PTX@HSA-lipos group was(3.126±0.68)g,with significant difference(F=28.36,P<0.05).CONCLUSION Albumin modified liposomes are a kind of drug delivery system with high efficiency,low toxicity and targeting to tumor tissue.

关 键 词：脂质体 人血清白蛋白修饰 前体药物 紫杉醇 肿瘤靶向性 

分 类 号：R944[医药卫生—药剂学]