VEGFRⅡ抗体介导多西他赛纳米脂质体在荷瘤小鼠体内的药动学  

Pharmacokinetics of VEGFRⅡantibody-mediated docetaxel-loaded nanoliposomes in tumor-bearing mice

作　　者：陈颖[1] 吴琳[1] 刘玮[1] 杨益 陈伟 张歆[4] CHEN Ying;WU Lin;LIU Wei;YANG Yi;CHEN Wei;ZHANG Xin(Department of Pharmacy,the Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China;Department of Pharmacy,the Third People′s Hospital of Zhenjiang,Zhenjiang 212001,China;Department of Pharmacy,the Fourth People′s Hospital of Zhenjiang,Zhenjiang 212001,China;Department of Ultrasound,the Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China)

机构地区：[1]江苏大学附属医院药剂科,镇江212001 [2]镇江市第三人民医院药剂科,镇江212001 [3]镇江市第四人民医院药剂科,镇江212001 [4]江苏大学附属医院超声医学科,镇江212001

出　　处：《西北药学杂志》2020年第6期876-881,共6页Northwest Pharmaceutical Journal

基　　金：2018年度镇江市重点研发计划(社会发展)项目(编号:SH2018034)。

摘　　要：目的制备血管内皮细胞生长因子受体Ⅱ(VEGFRⅡ)抗体介导的多西他赛纳米脂质体,并考察其在荷瘤小鼠体内的药动学及组织分布特性。方法采用薄膜分散-挤出法制备多西他赛纳米脂质体,再通过共同孵化方式将VEGFRⅡ-聚乙二醇2000-磷脂酰乙醇胺(VEGFRⅡ-mPEG2000-DSPE)包被在纳米脂质体表面,制备成VEGFRⅡ抗体介导多西他赛纳米脂质体;测定纳米脂质体的粒径分布和Zeta电位,用透射电镜观察纳米脂质体的微观结构;考察VEGFRⅡ抗体介导多西他赛纳米脂质体在pH值为7.4的磷酸盐缓冲液(PBS)和血浆中的释放情况;体内实验研究了VEGFRⅡ抗体介导多西他赛纳米脂质体在荷瘤小鼠体内的药动学与组织分布。结果制备的VEGFRⅡ抗体介导多西他赛纳米脂质体的平均粒径为233.6±10.5 nm,Zeta电位为-10.1±0.5 mV,在透射电镜下可观察到VEGFRⅡ抗体介导多西他赛纳米脂质体呈球状或类球状分布;体外药物释放结果显示,VEGFRⅡ抗体介导多西他赛纳米脂质体在pH值为7.4的PBS中释放较缓慢,在血浆中释放较快;VEGFRⅡ抗体介导多西他赛纳米脂质体在荷瘤小鼠体内的血药质量浓度时间曲线下面积(AUC_(0-t))和半衰期(t_(1/2))分别为多西他赛注射剂的3.3和2.1倍;VEGFRⅡ抗体介导多西他赛纳米脂质体在小鼠的肝、脾和肿瘤组织的相对摄取率分别为4.9,7.5和19.5。结论本研究制备的VEGFRⅡ抗体介导多西他赛纳米脂质体能显著延长药物在体内的滞留时间,并对肝、脾和肿瘤组织具有良好的靶向性,可提高药物疗效,降低毒性和不良反应。Objective To prepare docetaxel-loaded nanoliposomes mediated by vascular endothelial cell growth factor receptorⅡ(VEGFRⅡ)antibody(VEGFRⅡDoc-loaded Nlips),and to investigate their pharmacokinetics and tissue distribution characteristics in tumor-bearing mice.Methods The docetaxel-loaded nanoliposomes were prepared by thin film dispersion-extrusion method,and then VEGFRⅡ-mPEG2000-DSPE was coated on the surface of nanoliposomes by co-incubation method.The particle size distribution and Zeta potential of the VEGFRⅡDoc-loaded Nlips were measured,and the microstructure was observed under a transmission electron microscope.The drug release of VEGFRⅡDoc-loaded Nlips in pH 7.4 phosphate buffer and plasma was investigated.The pharmacokinetics and tissue distribution of VEGFRⅡDoc-loaded Nlips in tumor-bearing mice were studied in vivo.Results The average particle diameter of VEGFRⅡDoc-loaded Nlips was 233.6±10.5 nm,and the Zeta potential was-10.1±0.5 mV.Under transmission electron microscopy,it was observed that VEGFRⅡDoc-loaded Nlips were spherical or spheroid-like.The drug release in vitro showed that VEGFRⅡDoc-loaded Nlips were released slowly in pH 7.4 PBS,and released faster in plasma.The AUC 0-t and t 1/2 of VEGFRⅡDoc-loaded Nlips were 3.3 and 2.1 times higher than those of docetaxel injection,respectively.The relative uptake rates of VEGFRⅡDoc-loaded Nlips in liver,spleen,and tumor tissues of mice were 4.9,7.5 and 19.5.Conclusion The VEGFRⅡDoc-loaded Nlips could significantly prolong the drug retention time,and showed good targeting for liver,spleen and tumor tissues,which could improve the effect of drug treatment and reduce toxic and side effects.

关 键 词：血管内皮细胞生长因子受体Ⅱ抗体 纳米脂质体 薄膜分散-挤出法 靶向性 

分 类 号：R94[医药卫生—药剂学]