π-π堆积的氧化还原型阿霉素脂质体的制备与抗肿瘤活性评价  

Preparation and Antitumor Activity of DOX-Loaded Liposomes withπ-π Stacking and Redox-release Triggering

作　　者：单琪 孙东起 郑海涛 刘钧华 姚子涵 祝艳平 杜源[1] 张雷明[1] 凌龙兵 SHAN Qi;SUN Dong-qi;ZHENG Hai-tao;LIU Jun-hua;YAO Zi-han;ZHU Yan-ping;DU Yuan;ZHANG Lei-ming;LING Long-bing(School of Pharmacy,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drug in Universities of Shandong,State Key Laboratory of Long-acting and Targeting Drug Delivery System,Yantai University,Yantai,264005,China)

机构地区：[1]烟台大学药学院,新型制剂与生物技术药物研究山东省高校协同创新中心,长效和靶向制剂国家重点实验室,山东烟台264005

出　　处：《烟台大学学报（自然科学与工程版）》2022年第2期176-183,共8页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：山东省自然科学基金资助项目(ZR2020QH354);国家级大学生创新训练项目(S202011066013)。

摘　　要：为了合成π-π堆积的氧化还原型磷脂酰胆碱(Pyr-SS-PC),并制备“高载药量和促释放”阿霉素脂质体(DOX/Pyr-SS-PC Lips),对脂质体粒径、包封率、体外释放和稳定性等物化性质进行了研究,采用MTT法评价该脂质体对3种人类肿瘤细胞的体外细胞毒性,以荷MCF-7乳腺癌Balb/c裸鼠为肿瘤模型考察该脂质体的体内抗肿瘤活性。结果显示,通过π-π堆积作用,该脂质体能高效地包载DOX,其包封率(EE)达85.62%,且具有明显的氧化还原释药特性;DOX/Pyr-SS-PC Lips能够抑制肿瘤细胞株增殖,呈浓度依赖性关系;动物实验表明,功能化脂质体的抗肿瘤活性优于游离DOX,毒副作用小。本研究初步证明,基于Pyr-SS-PC磷脂制备的脂质体能增加药物的载药量和稳定性,实现药物在肿瘤组织响应释放,显示出较好的抗肿瘤活性。A new type of phosphatidylcholine(Pyr-SS-PC)lipid is designed for liposomal doxorubicin preparation(DOX/Pyr-SS-PC Lips)with redox-sensitivity and ultra-high loading byπ-πstacking effect.Due to the amphiphilicity,these liposomes are prepared by ultrasonic dispersion method and their physicochemical properties including size,loading efficiency,colloid stability and release profile are investigated in detail.To further assess in vivo and in vivo anti-tumor activity of liposomes,MTT assay is used towards three types of human tumor cells while MCF-7 tumor-bearing Balb/c nude mice model is used for in vivo evaluation.The results show that the liposomes can efficiently encapsulate the anticancer agent of DOX with the EE%up to 85.62%byπ-πstacking effect.With redox-sensitivity and sustained release profiles,DOX/Pyr-SS-PC Lips inhibit the proliferation of tumor cell lines in a concentration-dependent relationship,as demonstrated by MTT assay.More importantly,the developed liposomes loaded DOX display the enhanced antitumor activity while reducing side effect in MCF-7 tumor-bearing Balb/c nude mice model.Pyr-SS-PC lipid is used in liposomal drug carriers for the first time,and the Pyr-SS-PC Lips can enhance the drug loading and in vivo stability with redox-sensitivity,thereby exhibiting good anti-tumor activity.

关 键 词：Π-Π堆积 载药量 阿霉素脂质体 响应释药 肿瘤治疗 

分 类 号：R94[医药卫生—药剂学]