通脉方药效组分纳米晶自稳定Pickering乳剂的制备、表征及Caco-2细胞模型评价  

Nanocrystals self-stabilized Pickering emulsion loaded with active components of Tongmai prescription:preparation,characterization and evaluation by Caco-2 cell model

作　　者：张继芬[1] 叶鑫 王艳华 徐晓玉[1] 易涛 ZHANG Ji-fen;YE Xin;WANG Yan-hua;XU Xiao-yu;YI Tao(College of Pharmaceutical Sciences,Southwest University,Chongqing 400716,China;Faculty of Health Sciences and Sports,Macao Polytechnic University,Macao 999078,China)

机构地区：[1]西南大学药学院,重庆400716 [2]澳门理工大学健康科学及体育学院,中国澳门999078

出　　处：《药学学报》2023年第1期208-216,共9页Acta Pharmaceutica Sinica

基　　金：重庆市中医药重点建设学科西南大学中医康复学资助项目(2021-4322190044);澳门理工大学资助研究项目(RP/ESCSD-01/2020);澳门科学技术发展基金资助项目(001/2016/A1)。

摘　　要：将药物纳米晶自稳定Pickering乳液(NSSPE)应用于中药复方,研究NSSPE对复方中不同溶解性和渗透性成分口服吸收的影响,很有意义。本研究以通脉方主要药效成分葛根素、阿魏酸、丹酚酸B和丹参酮ⅡA组合物的纳米晶为固体微粒稳定剂,以川芎油∶Labrafil M 1944 CS为油相,采用高压均质法制备中药复方NSSPE。体外表征结果显示, NSSPE中药效组分纳米晶吸附于川芎油的油滴表面,较纳米晶混悬液和空白乳均具有更好的物理稳定性;NSSPE中葛根素、阿魏酸、丹酚酸B和丹参酮ⅡA在乳滴表面的吸附率分别15.40%±3.19%、15.39%±5.07%、10.97%±3.70%和31.51%±1.60%。Caco-2细胞模型研究显示,固体药效成分制备成纳米晶混悬液后,葛根素和丹参酮ⅡA的细胞摄取与转运都显著提高;纳米晶混悬液与川芎油制备成NSSPE后,阿魏酸、藁本内酯和丹参酮ⅡA的Caco-2细胞摄取量较纳米晶混悬液/油的物理混合物又进一步提高,藁本内酯和丹参酮ⅡA的跨膜转运也极显著提高。细胞转运机制主要是被动扩散和小窝蛋白介导的内吞, NSSPE的微观结构是影响其吸收机制的主要因素。本研究表明, NSSPE可应用于成分复杂、性质差异大的中药复方,药物纳米晶吸附于微米粒径的油滴表面形成“微”“纳”协同的微观结构,不仅能提高乳液的物理稳定性,还能促进各成分的细胞摄取和转运,有希望成为有潜力的中药复方口服新剂型。It is of great significance to apply the nanocrystals self-stabilized Pickering emulsion(NSSPE) to traditional Chinese medicine(TCM) compounds,and to study the effect of NSSPE on the oral absorption of various components with different solubility and permeability.In the study,NSSPE of Tongmai prescription was prepared by the high pressure homogenization method with nanocrystals of main active components(puerarin,ferulic acid,salvianolic acid B and tanshinone IIA) of Tongmai prescription as solid particle stabilizers and a mixture of Ligusticum chuanxiong essential oil and Labrafil M 1944 CS as oil phase.The NSSPE had better physical stability than nanocrystals suspension and blank emulsion.The adsorption of nanocrystals on the surface of oil droplets was confirmed by scanning electron microscopy and fluorescence microscopy.The surface adsorption rates of puerarin,ferulic acid,salvianolic acid B and tanshinone Ⅱ A in NSSPE were 15.40% ± 3.19%,15.39% ±5.07%,10.97% ± 3.70% and 31.51% ± 1.60%,respectively.When solid active components were prepared into nanocrystals suspension,the cellular uptake and transport across Caco-2 cells were increased significantly for puerarin and tanshinone IIA.The uptake rates of ferulic acid,ligustilide and tanshinone IIA in NSSPE were further increased compared with the physical mixture of nanocrystals suspension and oil,and the transports of ligustilide and tanshinone IIA were also significantly improved.The main absorption mechanisms of NSSPE were passive diffusion and caveolin-mediated endocytosis,which were determined mainly by the microstructure of NSSPE.In conclusion,NSSPE could be applied to complicated TCM.The "micro" and "nano" synergistic microstructure with drug nanocrystals adsorbed on the surface of micron-sized oil droplets could not only improve the physical stability of NSSPE,but also promote the absorption of various components in NSSPE,which made NSSPE a promising oral drug delivery system for TCM.

关 键 词：Pickering乳液 纳米晶 葛根 丹参 川芎 口服 

分 类 号：R943[医药卫生—药剂学]