叶酸壳聚糖姜黄素pH敏感脂质体的制备及靶向性研究  

Preparation of folic acid chitosan curcumin pH sensitive liposomes and investigation of their targeting effect

作　　者：刘小芳 吴仪君 石玮玮 阎芳 LIU Xiao-fang;WU Yi-jun;SHI Wei-wei;YAN Fang(College of Pharmacy,Weifang Medical College,Weifang 261053,China)

机构地区：[1]潍坊医学院药学院,潍坊261053

出　　处：《中国新药杂志》2018年第19期2315-2321,共7页Chinese Journal of New Drugs

基　　金：山东省医药卫生科技发展计划项目(2015ws0057);山东省中医药科技发展计划项目(2015-229);潍坊市科学技术发展计划项目(2015ws039)

摘　　要：目的:制备叶酸壳聚糖姜黄素pH敏感脂质体(FA-CS-Cur-pH-Lip),考察其理化性质及靶向性。方法:首先制得叶酸偶联壳聚糖(FA-CS),通过离子交联法使其包覆姜黄素pH敏感脂质体(Cur-pH-Lip)制得FA-CS-Cur-pH-Lip。考察其包封率、平均粒径、分散度、Zeta电位、形态及体外释药特性。通过MTT法和细胞摄取实验验证其靶向性。结果:制备的FA-CS-Cur-pH-Lip电镜下呈球形或近球形,平均粒径347.6 nm,多分散系数(PDI)0.170,Zeta电位为37.9 m V,包封率为95.6%。FA-CS-Cur-pH-Lip在PBS(pH 7.4和5.5)释放介质中48 h的Cur累积释放率分别为58.14%和96%,表现出很强的pH敏感性能。FA-CS-Cur-pH-Lip对MCF-7细胞和A549细胞增殖抑制作用强,且具有明显的叶酸受体靶向性。结论:本研究成功制得具有主动靶向和pH敏感特性的FA-CS-Cur-pH-Lip,为进一步研究其体内抗肿瘤作用奠定了基础。Objective： To prepare folic acid-conjugated chitosan-coated curcumin pH-sensitive liposomes（ FA-CS-Cur-pH-Lip） and investigate their physical and chemical properties and targeting effect. Methods： FA-CSCur-pH-Lip was prepared by ionic cross-linking method with folate-coupled chitosan（ FA-CS） and curcumin pH-sensitive liposomes（ Cur-pH-Lip）. The entrapment efficiency,average particle size,dispersion,Zeta-potential,morphology and drug release from FA-CS-Cur-pH-Lip in vitro were monitored. The targeting effect was verified by MTT assay and cell uptake assay. Results： The obtained FA-CS-Cur-pH-Lips were spherical or nearly spherical under electron microscope with average size of 347. 6 nm,polydispersity factor（ PDI） of 0. 170,Zeta potential of37. 9 m V and entrapment efficiency of 95. 6%. The results of drug release test showed that FA-CS-Cur-pH-Lip released 58. 14% Cur in pH 7. 4 PBS and 96% Cur in pH 5. 5 PBS after 48 h of incubation and showed stronger pH response. FA-CS-Cur-pH-Lip had strong inhibitory effect on the proliferation of MCF-7 cells and A549 cells,and had obvious folate receptor targeting effect. Conclusion： In this study,FA-CS-Cur-pH-Lip with active targeting and pH-sensitive properties was successfully prepared,which is expected to provide the basis for further investigation of its antitumor effect in vivo.

关 键 词：叶酸 壳聚糖 姜黄素 胆固醇琥珀酸单酯 pH敏感脂质体 主动靶向 

分 类 号：R943[医药卫生—药剂学]