近红外光响应性多烯紫杉醇主动靶向脂质体的制备及其体外抗肿瘤活性  

Preparation and in vitro Antitumor Activity of Near-infrared Light Responsive Docetaxel Active Targeting Liposomes

作　　者：祝侠丽[1] 李玲华 王莎莎 王白燕[2] 关延彬[1] 贾永艳[1] ZHU Xiali;LI Linghua;WANG Shasha;WANG Baiyan;GUAN Yanbin;JIA Yongyan(Colloge of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Colloge of Basic Medical,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学药学院,郑州450046 [2]河南中医药大学基础医学院,郑州450046

出　　处：《医药导报》2021年第8期1094-1099,共6页Herald of Medicine

基　　金：国家自然科学基金资助项目(81803740);河南省高等学校青年骨干教师培养项目资助项目(2016 GGJS-081)。

摘　　要：目的以亲水性纳米硫化铜(PVP/CuS)为光敏剂,甘草次酸(GA)为肿瘤靶向分子,多烯紫杉醇(DTX)为模型药物,制备近红外光响应性多烯紫杉醇主动靶向脂质体(GA-DTX-PVP/CuS-Lip),并研究其理化性质和体外抗肿瘤活性。方法采用薄膜分散法制备GA-DTX-PVP/CuS-Lip,利用透射电镜观察微观形态,激光粒度仪测定粒径和Zeta电位,超滤-离心法测定包封率。结合808 nm激光照射进行光热转换试验,采用透析法进行37℃和45℃下的体外释放度试验,并选择人肝癌细胞SMMC-7721细胞为模型进行细胞抑制率试验。结果透射电镜下观察到GA-DTX-PVP/CuS-Lip为类圆球形结构,大小较为均匀,平均粒径和电位分别为(226.73±0.17)nm和(-4.05±0.57)mV,包封率和载药量分别为(96.33±0.21)%和(6.63±0.39)%。808 nm激光照射下,GA-DTX-PVP/CuS-Lip具有明显的光热转换效应。体外释放度试验结果显示与DTX溶液比较,GA-DTX-PVP/CuS-Lip具有明显的缓释特征,45℃下的释药速度明显高于37℃下的释药速度。细胞实验结果显示,GA-DTX PVP/CuS-Lip结合808 nm激光照射对SMMC-7721细胞的抑制率增高。结论GA-DTX-PVP/CuS-Lip的制备工艺稳定可行,可为进一步进行肿瘤光热化联合治疗提供一定的理论依据。Objective Using hydrophilic nano copper sulfide(PVP/CuS)as a photosensitizer,glycyrrhetinic acid(GA)as a tumor targeting molecule,docetaxel(DTX)as a model drug,a near-infrared light responsive active targeting liposomes(GA-DTX-PVP/CuS-Lip)was prepared,and its physical chemical properties and in vitro antitumor activity were also studied.Methods The thin film dispersion method was used to prepare GA-DTX-PVP/CuS-Lip,and its microstructure was observed under transmission electron microscope.The particle size and zeta potential were measured by laser granulometer.The encapsulation efficiency and drug loading ratio were determined using ultrafiltration and centrifugation method.Combined with 808 nm laser irradiation,the light-thermal conversion experiment was carried out.The in vitro drug release test was carried out by using the dialysis method at 37℃and 45℃.The in vitro antitumor activity of GA-DTX-PVP/CuS-Lip against SMMC-7721 cells with or without 808 nm laser irradiation was also measured.Results GA-DTX-PVP/CuS-Lip was observed to be spherical with uniform size under TEM.The particle size and Zeta potential were(226.73±0.17)nm and(-4.05±0.57)mV,respectively.The encapsulation efficiency and drug loading ratio were(96.33±0.21)%and(6.63±0.39)%,respectively.GA-DTX-PVP/CuS-Lip had a significant photothermal conversion effect under laser irradiation at 808 nm in a concentration and time-dependent manner.The drug release test showed that compared with DTX solution,GA-DTX-PVP/CuS-Lip had sustained and temperature-dependent release characteristics,and the release rate at 45℃was significantly higher than that at 37℃.GA-DTX-PVP/CuS-Lip had higher inhibitory effect on SMMC-7721 cells when combined with 808 nm laser irridation.Conclusion The preparation process of GA-DTX-PVP/CuS-Lip is stable and feasible,which can provide a theoretical basis for further tumor photothermal therapy.

关 键 词：多烯紫杉醇 甘草次酸 主动靶向脂质体 纳米硫化铜 光热治疗 肿瘤靶向 

分 类 号：R735.7[医药卫生—肿瘤]