藤黄酸长循环纳米粒的制备及其抗肿瘤作用研究  

Preparation and anti-tumor activity study of long-circulating,self-assembled gambogic acid nanoparticles

作　　者：郭鸣睿 王芳[1] 陈立江[1,2] 欧阳德方 刘宇 梁啸[1] 张国林[4] 张金凤[1] 刘宏生 GUO Ming-rui;WANG Fang;CHEN Li-jiang;OUYANG De-fang;LIU Yu;LIANG Xiao;ZHANG Guo-lin;ZHANG Jin-feng;LIU Hong-sheng(Liaoning University College of Pharmacy,Shenyang 110036,China;State Key Labo,Ratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences（ICMS）,University of Macao,Macao 999078,China;Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning Province,Shenyang 110036,China;Collegeof Chemistry,Liaoning University,Shenyang 110036,China)

机构地区：[1]辽宁大学药学院,沈阳110036 [2]辽宁省生物大分子计算模拟与信息处理工程技术研究中心,沈阳110036 [3]澳门大学中药质量研究国家重点实验室,澳门999078 [4]辽宁大学化学院,沈阳110036

出　　处：《中国新药杂志》2018年第14期1639-1644,共6页Chinese Journal of New Drugs

基　　金：辽宁省教育厅创新团队项目(LT2015011);辽宁省教育厅科学研究项目(L2015192);沈阳市科技计划项目(F16-205-1-44);辽宁省教育厅创新人才研究项目(LR2017065)

摘　　要：目的:本研究合成了两亲性三嵌段聚合物聚己内酯-聚乙二醇-聚己内酯(polycaprolactone-polyethylene glycol-polycaprolactone,PCL-PEG-PCL)用以包载藤黄酸形成纳米粒,考察了其制备工艺,体外抗肿瘤活性和药动学。方法:采用聚合反应合成两亲性三嵌段聚合物PCL-PEG-PCL,以此作为胶束载体材料,采用薄膜-水化-超声法制备载藤黄酸的PCL-PEG-PCL自组装纳米粒,并对载药胶束的包封率、粒径、体外释放率和体外抗肿瘤活性等性质进行了考察。结果:本研究所制备的载藤黄酸纳米粒粒径为226.5 nm,PDI为0.208,包封率为92.69%。藤黄酸自组装纳米粒在0.5 h内药物的释放量小于40%,没有出现明显的突释现象。体外抗肿瘤活性实验结果显示载药纳米粒在24 h内抗肿瘤活性低于原料药,但在36 h后载药纳米粒组抗肿瘤活性高于原料药。结论:藤黄酸自组装纳米粒具有良好的体外抗肿瘤作用,具有一定的缓释效果和长循环效果。Objective： To synthesize amphiphilic triblock polymer polycaprolactone-polyethylene glycolpolycaprolactone（ PCL-PEG-PCL） as carriers of gambogic acid（ GA） and study its preparation process,antitumor activity and pharmacokinetics. Methods： The PCL-PEG-PCL was synthesized by polymerization reaction and was used as nanoparticle materials to obtain GA-loaded nanoparticles. The encapsulation efficiency,particle size,release rate and anti-tumor activities in vitro were investigated. Results： The particle size of nanoparticles with optimal formulation and process was around 226. 5 nm and the PDI was 0. 208. The encapsulation efficiency was above92%. The release of GA-loaded nanoparticles was less than 40% in 0. 5 h and showed no obvious burst release.The cell inhibition rate of GA-loaded micelles was lower than that of GA after 24 h but higher than it after 36 h.Conclusion： The GA-loaded nanoparticles demonstrated good long-circulating activities and slow-release characteristic in vitro and the GA-loaded nanoparticles showed good anti-tumor activities.

关 键 词：聚己内酯-聚乙二醇-聚己内酯 自组装纳米粒 藤黄酸 抗肿瘤 

分 类 号：R943[医药卫生—药剂学]