摘要
药物联合可有效增强抗肿瘤作用,减少药物剂量,提高用药安全性,采用纳米载体进行药物共载可有效避免不同药物的体内传递行为差异。雷公藤甲素和雷公藤红素是"毒效双重"中药雷公藤的主要抗肿瘤活性成分,现代研究表明两者联合可显著增强抗肿瘤作用,但受限于水溶解性差、肿瘤组织递送率低等不足。本研究制备了一种将雷公藤甲素与红素共载的红细胞膜仿生脂质体,开展形貌、粒径、电位、药物释放、血清稳定性等性质表征,对比考察该仿生脂质体的免疫原性及其在人源肝癌HepG2细胞的摄取行为、抗细胞增殖能力。动物福利和实验过程均遵循成都中医药大学动物伦理委员会的规定。结果显示,本研究所制备的雷公藤甲素-红素的红细胞膜仿生共载脂质体(C+T/RBCm@Lip),平均粒径119.12±2.78 nm,呈"核-壳"结构的球形,zeta电位值为-16.9±1.2 mV,体外释药行为缓慢,包膜过程可较好保持红细胞膜蛋白特性,在血清中稳定性较好,可有效躲避巨噬细胞的识别与清除,且不引起体内免疫原性。共载仿生脂质体在HepG2肝癌细胞摄取作用较未包被细胞膜脂质体增强,且对HepG2细胞增殖的抑制作用增强。综上,本研究所制备红细胞仿生脂质体有利于雷公藤甲素和红素的抗肿瘤共递送,增强对HepG2肝癌细胞生长的抑制作用,为中药雷公藤抗肿瘤应用提供新思路。
Drug combination can effectively enhance the anti-tumor effect,reduce the drug dose,and improve medication safety.The use of nano-carrier for drug co-delivery can effectively avoid the differences in drug delivery behavior in vivo.Triptolide and celastrol are the main anti-tumor active components of Tripterygium wilfordii Hook f.Modern studies have shown that the combination of triptolide and celastrol can significantly enhance the antitumor effect,but they are limited by poor water solubility and low tumor tissue delivery rate.In this study,a biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol was prepared to characterize the morphology,particle size,potential,drug release,serum stability,and other properties.The immunogenicity,uptake behavior,and anti-cell proliferation ability of the biomimetic liposome was compared.All the animal experiments were carried out in accordance with protocol evaluated and approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine(Chengdu,China).The results showed that the biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol(C+T/RBCm@Lip)in this study had an average particle size of119.12±2.78 nm and a spherical"core-shell"structure.The zeta potential value was-16.9±1.2 mV,and the drug release behavior in vitro was slow.In addition,the process of coating the cell membrane maintained the characteristics of erythrocyte membrane protein,had good stability in serum,and could effectively avoid the recognition and clearance of macrophages,without causing immunogenicity in vivo.The uptake effect of co-loaded biomimetic liposomes on HepG2 hepatocellular carcinoma cells was enhanced compared with that of uncoated cell membrane liposomes,and the inhibitory effect on proliferation of HepG2 cells was enhanced.In conclusion,the biomimetic liposomes coated with erythrocyte membrane prepared in this study is beneficial to the anti-tumor delivery of triptolide and celastrol,and could enhance the inhibitory effect
作者
钟雪梅
鲜静
石金凤
吴亿晗
陈佳美
林洁
章津铭
邹亮
ZHONG Xue-mei;XIAN Jing;SHI Jin-feng;WU Yi-han;CHEN Jia-mei;LIN Jie;ZHANG Jin-ming;ZOU Liang(Pharmacy School,State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;College of Pharmacy,Chengdu Medical College,Chengdu 610500,China;School of Food and Biological Engineering,Chengdu University,Chengdu 610106,China)
出处
《药学学报》
CAS
CSCD
北大核心
2021年第12期3252-3260,共9页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81973662)
四川省杰出青年科技人才项目(2019JDJQ0049)。
