摘要
目的制备雷公藤甲素(triptolide,TP)柔性纳米脂质体(flexible nanoliposomes,FNLs),并对其体外抗炎活性及透皮性能进行考察。方法以(2,3-二油酰基-丙基)-三甲基氯化铵(N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium me-thyl-sulfate,DOTAP)、胆固醇(cholesterol,CHOL)为主要囊材,用薄膜分散法制备TP-FNLs,并对其进行理化性质表征;以RAW 264.7细胞为模型,考察TP-FNLs的细胞摄取及抗炎活性;用Franz扩散池法考察TP-FNLs经大鼠离体皮肤的累积渗透量和滞留量。结果TP-FNLs的粒径为(178±13)nm,多分散性系数(polymer dispersity index,PDI)为(0.237±0.021),Zeta电位为(12.39±1.80)mV,包封率为(56.3%±4.1%)。在透射电子显微镜下,TP-FNLs呈梭形,且具有良好的变形性。TP-FNLs具有较高的稳定性,并具有一定的pH响应释药特性。TP-FNLs能够时间依赖性地被RAW 264.7细胞摄取,并可有效降低炎症因子的分泌。Franz扩散池结果显示,TP-FNLs中TP的36 h皮肤累积渗透量为(397.08±29.61)μg·cm^(-2),约为TP混悬液的4.5倍。36 h后TP-FNLs中TP的皮肤滞留量为(46.56±6.39)μg·cm^(-2),约为TP混悬液的4倍。结论TP-FNLs具有较好的稳定性,能环境响应性地发生释药,能有效降低RAW 264.7细胞炎症因子的分泌,且具有良好的透皮性能。
Objective Triptolide flexiblnano liposomes(TP-FNLs)were prepared and its anti-inflammatory activity and transdermal properties were investigated in vitro.Methods TP-FNLs were prepared by thin film dispersion method with N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate(DOTAP)and cholesterol(CHOL)as the main materials,and their physicochemical properties were characterized.The cellular uptake and anti-inflammatory activity of TP-FNLs were investigated in RAW 264.7 cells.Franz method was used to investigate the cumulative penetration and retention of TP-FNLs through rat skin in vitro.Results The particle size of TP-FNLs was(178±13)nm,the polymer dispersity index(PDI)was(0.237±0.021),the Zeta potential was(12.39±1.80)mV,and the entrapment efficiency was(56.3%±4.1%).Transmission electron microscopy results showed that TP-FNLs had spindle shape and good deformability.TP-FNLs showed high stability and certain pH responsive drug release characteristics.TP-FNLs can be ingested by RAW 264.7 cells in a time-dependent manner,and can effectively reduce the expression of pro-inflammatory factors.The results of Franz showed that,after administration 36 hours,the skin cumulative penetration of TP in TP-FNLs was(397.08±29.61)μg·cm^(-2),and was about 4.5 times than that of free TP.The skin retention of TP in TP-FNLs was(46.56±6.39)μg·cm^(-2),and was about 4 times than that of free TP.Conclusion TP-FNLs have good stability and release TP in environmental responsiveness,they effectively reduce the expression of pro-inflammatory factors in RAW 264.7 cells,and have good transdermal properties.
作者
刘美秀
付林可
周丹
袁晓峰
韩江帆
叶威良
LIU Meixiu;FU Linke;ZHOU Dan;YUAN Xiaofeng;HAN Jiangfan;YE Weiliang(Department of Pharmaceutics and Pharmaceutical Administration,School of Pharmacy,Air Force Military Medical University,Xi'an 710032,China;Department of Gastroenterology,the First Affiliated Hospital of Air Force Medical University,Xi'an 710032,China;Department of Pharmacy,the Ninth Hospital of Xi'an,Xi'an 710054,China)
出处
《西北药学杂志》
CAS
2023年第6期94-99,共6页
Northwest Pharmaceutical Journal
基金
国家自然科学基金青年科学基金项目(编号:81901869)
陕西省自然科学基础研究计划项目(编号:2021JQ-923)。
关键词
雷公藤甲素
柔性脂质体
抗炎活性
透皮给药
累积渗透量
triptolide
flexible liposome
anti-inflammatory activity
transdermal administration
cumulative penetration
