微乳载药体系对α-倒捻子素抗滑膜细胞增殖的增效作用研究  

Microemulsion as the drug delivery system improves inhibitory effects of α-mangostin on synovium

作　　者：郭辉霞 陶梦情 左坚[2] 汪魏平[2] GUO Huixia;TAO Mengqing;ZUO Jian;WANG Weiping(Department of Pharmacy, the Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, Anhui, China;Department of Pharmacy, Yijishan Hospital of Wannan Medical College, Wuhu 241000, Anhui , China)

机构地区：[1]皖南医学院第二附属医院药剂科 [2]皖南医学院弋矶山医院药剂科

出　　处：《中国临床药理学与治疗学》2017年第11期1227-1231,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省卫生计生委中医药科研课题项目(2016zy37)

摘　　要：目的:α-倒捻子素(α-mangostin,MG)是一种具有潜在的抗风湿活性的多酚。为改善其药动学特性,我们制备了MG的微乳体系(MG-loaded microemulsion,MG-ME),本研究拟进一步揭示MG-ME可能存在的增效性特征。方法:本研究分析比较了MG-ME相对于其溶液在细胞摄取率、增殖抑制率、通路调控能力及体内关节保护效率等方面的差异。体外实验采用类风湿关节炎成纤维样滑膜细胞(HFLS-RA)为研究对象,MG在细胞内分布采用HPLC法测定,细胞活力采用MTT法测定,通路的调控作用采用Western blot法检测,体内药效以对佐剂性关节炎(adjuvant-induced arthritis,AA)大鼠的治疗效果为依据。结果:微乳显著提高了细胞对于MG的摄取,强化了MG对HFLS-RA细胞中p38和NF-κB信号通路的调控,并对该细胞的体外增殖产生更为高效的抑制作用;同时相对于溶液体系,MG-ME进一步改善了药物对AA大鼠的关节保护作用。结论:结果表明微乳能增强滑膜组织对于MG的摄取,提高滑膜细胞对于药物刺激的敏感性,从而切实提高药物的体内疗效,是极具潜力且值得深入研究的抗风湿药物的有效载体。AIM：α-Mangostin （MG） is a xanthone with antirheumatic effect.To improve the pharmacokinetic performance,we prepared MG loaded microemulsion （MG-ME）.This study was designed to evaluate its potential improvements to therapeutic efficacy.METHODS：Intakes of MG by cells were determined by HPLC.Inhibition on proliferation of cells was assessed by MTT method.Western blot was employed to investigate modulation of MG on transduction pathways.The therapeutic efficacy of MG was evaluated based on the effects on adjuvant induced arthritis in rats.RESULTS：Microemulsion improved the intakes of MG in human fibroblast-like synoviocyte rheumatoid arthritis （HFLS-RA） cells,which resulted in the enhanced inhibition on proliferation of cells and modulations on p38 and NF-κB signalings.Also,this delivery system was found augmenting the protection on joints in vivo.CONCLUSION：Microemulsion improved the intakes of MG and the sensitivity of drug stimulation in HFLS-RA cells.It enhances the dru efficacy in vivo and is a promising delivery system for antirheumatic agents.

关 键 词：α-倒捻子素 HFLS-RA细胞 滑膜 类风湿性关节炎 微乳 

分 类 号：R965.2[医药卫生—药理学]