摘要
目的制备羟丙基三甲基氯化铵壳聚糖(HACC)修饰的艾塞那肽固体脂质纳米粒(HACC-Exenatide-SLNs),并体外评价其转运能力。方法采用复乳化溶剂挥发法制备Exenatide-SLNs和HACC-Exenatide-SLNs。取纳米粒悬液,高分辨透射电镜下观察形态,激光粒度仪测其粒径及表面电位,HPLC法测算载药量。建立黏膜滤泡相关上皮(FAE)单层细胞模型,将细胞分为三个组,分别加入艾塞那肽溶液(艾塞那肽溶液组)、Exenatide-SLNs混悬液(Exenatide-SLNs组)、HACC-Exenatide-SLNs混悬液(HACC-Exenatide-SLNs组),测算药物转运率并检测细胞中的紧密连接蛋白Claudin-1。结果HACC-Exenatide-SLNs组粒径低于Exenatide-SLNs组,表面电位由负电位变为正电位,载药量略低于Exenatide-SLNs组(P均<0.05)。HACC-Exenatide-SLNs组药物转运率高于艾塞那肽溶液组,且HACC-Exenatide-SLNs组高于Exenatide-SLNs组(P均<0.01)。HACC-Exenatide-SLNs组Claudin-1相对表达量低于艾塞那肽溶液组、Exenatide-SLNs组(P均<0.05)。结论成功制备HACC-Exenatide-SLNs,HACC修饰后纳米粒的药物转运能力提高,可促进药物从旁路途径转运。
Objective To prepare exenatide-loaded solid lipid nanoparticles(HACC-Exenatide-SLNs)modified by hydroxypropyl trimethyl ammonium chloride(HACC),and to evaluate its in vitro cellular transport.Methods Exenadide-SLNs and HACC-Exenadide-SLNs were prepared by double emulsion solvent evaporation method.The morphology of nanpoparticle was observed under high resolution transmission electron microscope,the particle size and surface potential were measured by laser granularity meter,and the drug loading was measured by HPLC method.The single-layer cell model of mucosal follicle-associated epithelium(FAE)was established and was divided into three groups.Exenadide solution(exenadide solution group),exenatide-SLNs suspension(exenatide-SLNs group),and HACC-exenatide-SLNs suspension(HACC-Exenatide-SLNs group)were added to FAE models,respectively.The drug transparent rate and the tight junction associated protein Claudin-1 in cells were detected.Results The particle size of HACC-Exenatide-SLNs was smaller than that of Exenatide-SLNs,the surface potential changed from negative potential to positive potential,and the drug loading was slightly lower than that of Exenatide-SLNs(all P<0.05).The drug transparent rate in the HACC-Exenatide-SLNs group was higher than that in the Exenatide group,and the HACC-Exenatide-SLNs group was higher than the Exenadide-SLNs group(both P<0.01).The relative expression of Claudin-1 in the HACC-Exenatide-SLNs group was lower than that in the Exenatide group and the Exenatide-SLNs group(both P<0.05).Conclusion HACC-Exenatide-SLNs are successfully prepared,and the drug transport is improved after modification of HACC,indicating that HACC-Exenatide-SLNs can promote drug transport from bypass.
作者
董晶剑
沈斌
肖艳萍
曹青日
施丽丽
DONG Jingjian;SHEN Bin;XIAO Yanping;CAO Qingri;SHI Lili(Jiaxing College School of Medicine,Jiaxing 314001,China)
出处
《山东医药》
CAS
2019年第32期16-19,共4页
Shandong Medical Journal
基金
浙江省基础研究计划项目(LGF18H260008)
嘉兴市科技计划项目(2017AY33075)
关键词
艾塞那肽
固体脂质纳米粒
羟丙基三甲基氯化铵壳聚糖
药物转运
紧密连接蛋白
exenadide
solid lipid nanoparticles
hydroxypropyl trimethyl ammonium chloride
drug transport
tight junction associated protein
作者简介
第一作者:董晶剑(1984-),男,实验员,主要研究方向为生化化学与分子生物学。E-mail:jingjianwy@163.com;通信作者:施丽丽(1990-),女,实验员,主要研究方向为新型纳米制剂与口服制剂的研制。E-mail:wssll0@126.com。
