达卡巴嗪长循环脂质体的制备及体内抗肿瘤效应  

Preparation of long circulating liposomal dacarbazine and preliminary study on its antitumor effect in vivo

作　　者：王丽 朱九群[2] 龙超 何林[2] 董文娟 WANG Li;ZHU Jiuqun;LONG Chao;HE Lin;DONG Wenjuan(Nanchong Key Laboratory of Individualized Drug Therapy,Department of Pharmacy,Nanchong Central Hospital,Nanchong 637000,Sichuan,China;Department of Pharmacy,Sichuan Province People’s Hospital,Chengdu 610072,China;School of Medicine,University of Electronic Science and Technology of China,Chengdu 610072,China)

机构地区：[1]南充市中心医院药学部·个体化药物治疗重点实验室,四川南充637000 [2]四川省人民医院药学部,四川成都610072 [3]电子科技大学医学院,四川成都610072

出　　处：《西部医学》2021年第9期1388-1392,共5页Medical Journal of West China

基　　金：四川省科技计划重点研发项目(2017SZ0134)。

摘　　要：目的探讨达卡巴嗪长循环脂质体(PEGylated dacarbazine liposome,PEG-DTIC-LP)的制备及体内抗肿瘤效应。方法采用硫酸铵梯度法制备PEG-DTIC-LP,考察其包封率、载药量、形态、粒径、Zeta电位、稳定性、体外释药性等性质。建立荷黑色素瘤小鼠模型,将小鼠分为生理盐水组、空白脂质体组、DTIC溶液组、PEG-DTIC-LP组4组,每组6只,雌雄各半。于第1、3、5、7、9天按10 mg/kg给药剂量给生理盐水组小鼠尾静脉注射生理盐水,空白脂质体组尾静脉注射空白脂质体混悬液,DTIC溶液组尾静脉注射1mg/mL DTIC溶液,PEG-DTIC-LP组尾静脉注射1 mg/mL PEG-DTIC-LP混悬液。以肿瘤体积、小鼠体重、中位生存时间为评价指标,研究PEG-DTIC-LP的抗肿瘤效应。结果制备的PEG-DTIC-LP为半透明乳白色有蓝色乳光的液体;包封率为(60.41±2.47)%,载药量为(5.95±0.24)%;平均粒径为190nm,Zeta电位为53.8mV;放置7天后PEG-DTIC-LP包封率无显著变化(P>0.05),放置14天后包封率下降明显(P<0.05);PEG-DTIC-LP组荷瘤小鼠的肿瘤体积显著小于DTIC组与生理盐水组(P<0.05),但与空白脂质体组比较差异无统计学意义(P>0.05);中位生存时间PEG-DTIC-LP组>空白脂质体组>生理盐水组>DTIC溶液组(P<0.05);PEG-DTIC-LP组体重低于其余三组(P<0.05)。结论将达卡巴嗪制备成长循环脂质体有利于提高其抗肿瘤效应。Objective To prepare PEGylated long circulating dacarbazine liposome(PEG-DTIC-LP),and preliminarily study its antitumor effect in vivo.Methods The liposomes were prepared using the ammonium sulfate gradient method,and its entrapment efficiency,drug loading,morphology under electron microscope,particle size,zeta potential,stability and drug release behavior in vitro were investigated.Establish melanoma-bearing mouse models.The antitumor effect of PEG-DTIC-LP was studied using mouse tumor volume,body weight and median survival time as the indicators,and DTIC solution,saline and blank liposomes were used as the control groups.Results PEG-DTIC-LP was a translucent milky-white suspension with blue opalescence.The encapsulation efficiency was 60.41±2.47%and the drug loading was 5.95±0.24%.The average particle size was 190 nm,and the zeta potential was-53.8 mV.Compared with three control groups,the tumor volume of mice in PEG-DTIC-LP group was significantly smaller,and the median survival time was longer.Conclusion Long circulating liposome encapsulation is beneficial to improve the antitumor effect of DTIC.

关 键 词：达卡巴嗪 长循环脂质体 黑色素瘤 荷瘤小鼠 抗肿瘤效应 

分 类 号：R739.5[医药卫生—肿瘤]