血管内皮细胞生长因子受体Ⅱ抗体修饰的多西他赛脂质体的制备与药效学评价  

Preparation and pharmacodynamic evaluation of VEGFR II antibody-modified docetaxel-loaded liposomes

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

出　　处：《沈阳药科大学学报》2020年第9期782-788,共7页Journal of Shenyang Pharmaceutical University

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

摘　　要：目的制备由血管内皮细胞生长因子受体Ⅱ(vascular endothelial growth factor receptorⅡ,VEGFRⅡ)抗体修饰的多西他赛脂质体,并评价其对乳腺癌细胞MCF-7的体内外抗肿瘤效果。方法采用薄膜分散-挤出法制备多西他赛脂质体,再将血管内皮细胞生长因子受体Ⅱ-二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000(VEGFRⅡ-distearoyl phosphothanolamine-polyethyleneglycol 2000,VEGFRⅡ-mPEG2000-DSPE)连接物与脂质体共同孵化制备成VEGFRⅡ修饰的介导多西他赛脂质体,通过透射电镜观察其微观形态,粒度分析仪测定其粒径分布和zeta电位,并考察了多西他赛脂质体和VEGFRⅡ抗体修饰的多西他赛脂质体的体外释药特性;比较了多西他赛脂质体和VEGFRⅡ抗体修饰的多西他赛脂质体在体外和体内对乳腺癌细胞MCF-7的抗肿瘤效果。结果在透射电镜下可观察到多西他赛脂质体和VEGFRⅡ抗体修饰的多西他赛脂质体均呈球状或类球状分布,平均粒径分别为(226.2±16.4)nm和(233.6±10.5)nm,多聚分散系数(PdI)分别为(0.186±0.012)和(0.179±0.009),zeta电位分别为(-9.7±0.6)mV和(-10.1±0.5)mV;多西他赛脂质体和VEGFRⅡ抗体修饰的多西他赛脂质体在pH 7.4磷酸缓冲液中释药均较为缓慢;在体外多西他赛脂质体和VEGFRⅡ抗体修饰的多西他赛脂质体均能够有效地抑制乳腺癌细胞MCF-7生长,而在裸鼠体内VEGFRⅡ修饰的多西他赛脂质体抑制乳腺癌细胞MCF-7生长速度显著高于多西他赛脂质体。结论本研究制备的VEGFRⅡ抗体修饰的多西他赛脂质体对乳腺癌细胞MCF-7具有较强的抑制活性,VEGFRⅡ抗体修饰的多西他赛脂质体具有潜在的临床应用价值,值得进一步研究。Objective To prepare docetaxel-loaded liposomes(Doc-loaded Lipos)modified by vascular endothelial growth factor receptor II(VEGFR II)antibody and evaluate its anti-tumor effect on breast cancer cells MCF-7 in vitro and in vivo.Methods The Doc-loaded Lipos were prepared by thin film dispersion-extrusion method.The VEGFR II-mPEG2000-DSPE conjugate was co-incubated with liposomes to prepare VEGFR II antibody-modified docetaxel-loaded liposomes(VEGFR II Doc-loaded Lipos).The microscopic morphology was observed by transmission electron microscopy,and the particle size distribution and zeta potential were determined by laser diffraction particle size analyzer.The in vitro release characteristics of Doc-loaded Lipos and VEGFR II Doc-loaded Lipos were investigated.The anti-tumor effect of Doc-loaded Lipos and VEGFR II Doc-loaded Lipos in vitro and in vivo were compared by breast cancer cell MCF-7.Results Under transmission electron microscopy,Doc-loaded Lipos and VEGFR II Doc-loaded Lipos were observed to be spherical or globular,with an average particle size of(226.2±16.4)nm and(233.6±10.5)nm,PdI of(0.186±0.012)and(0.179±0.009),Zeta potential of(-9.7±0.6)mV and(-10.1±0.5)mV.The in vitro release of Doc-loaded Lipos and VEGFR II Doc-loaded Lipos were slowly in pH 7.4 PBS.The Doc-loaded Lipos and VEGFR II Doc-loaded Lipos could effectively inhibit the growth of breast cancer cells MCF-7 in vitro.However,VEGFR II Doc-loaded Lipos inhibited the growth of MCF-7 in breast cancer cells in nude mice significantly higher than Doc-loaded Lipos in vivo.Conclusion The VEGFR II Doc-loaded Lipos have good inhibitory activity for breast cancer cell MCF-7,which has potential clinical application value and deserves further study.

关 键 词：血管内皮细胞生长因子受体Ⅱ抗体 脂质体 薄膜分散-挤出法 抗肿瘤效果 

分 类 号：R94[医药卫生—药剂学]