摘要
枸橼酸托法替尼(tofacitinib citrate,TOF)能够对中至重度活动性类风湿性关节炎(Rheumatoid Arthritis,RA)产生较好的疗效,但因缺乏靶向性而易产生胃肠道等不良反应.为了增加其靶向性,减少不良反应,实验通过pH梯度法制备TOF脂质体,以包封率为评价指标,通过单因素法探究包封率的影响因素,确定优势处方.由体外释放结果可知,TOF脂质体在正常生理条件下的释药速度较慢.细胞活性实验结果表明,空白脂质体对巨噬细胞的活性几乎无影响.荧光成像实验结果可知,脂质体组关节部位的荧光强度明显强于游离组,说明脂质体可以增加药物在RA部位的富集,有利于药物靶向治疗RA.初步药效学结果显示,TOF脂质体能够更好地减轻RA足掌肿胀.综上所述,TOF脂质体具有良好的生物相容性和炎性关节部位的靶向性且抗RA效果良好.
Tofacitinib citrate(TOF) has a good therapeutic effect on moderate-to-severe active Rheumatoid Arthritis(RA),but it is easy to produce gastrointestinal and other adverse reactions due to lack of targeting.In order to increase its targeting ability and reduce adverse reactions,TOF liposomes(TOFL) were prepared by pH gradient method in this study.With the entrapment rate as the evaluation index,the influencing factors of the entrapment rate were explored by single factor method to determine the superior prescription.From the in vitro release results,TOF liposomes had a certain sustained release effect in pH7.4PBS.The results of MTT showed that blank liposomes(BL) had almost no effect on the activity of RAW264.7 cells and could be used as drug carrier.Fluorescence imaging experiment showed that the fluorescence intensity in joint of the liposome group was significantly stronger than the free group,indicating that liposome could increase the enrichment of drugs in the RA site,which was be beneficial for drug targeted treatment of RA.The preliminary pharmacodynamic results showed that TOFL could reduce the paw swelling of RA better than free TOF.In conclusion,TOFL had good biocompatibility,targeting at RA inflammatory joint,and good anti-RA effect.
作者
钱洋伟
舒幻
方宇镱
沈奇英
QIAN Yangwei;SHU Huan;FANG Yuyi;SHEN Qiying(School of Pharmacy,Hangzhou Normal University,Hangzhou 311121,China)
出处
《杭州师范大学学报（自然科学版）》
CAS
2023年第1期22-27,共6页
Journal of Hangzhou Normal University(Natural Science Edition)
基金
浙江省卫生健康科技计划青年人才项目(2022RC241)
2022年杭州师范大学“星光计划”项目
杭州师范大学2022—2023学年“本科生创新能力提升工程”项目。
关键词
枸橼酸托法替尼
脂质体
包封率
制备
评价
tofacitinib citrate
liposomes
encapsulation rate
preparation
evaluation
作者简介
通信作者:沈奇英(1981-),女,副教授,主要从事纳米给药系统研究.E-mail:qyshen718@hotmail.com。
