升麻苷H-1利用鼻腔嗅觉区鼻-脑通道进行鼻脑靶向给药的可行性  

Feasibility of nasal brain targeted drug delivery through the nose-brain channel in the nasal olfactory region using cimicifugoside H-1

作　　者：武密山[1] 赵素芝 高维娟 王茹[1] 韩红伟[1] 师旭亮[1] 

机构地区：[1]河北中医学院基础医学院方剂学教研室,河北省石家庄市050200 [2]石家庄市长安区胜北社区卫生服务中心,河北省石家庄市050041 [3]河北省心脑血管病中医药防治重点实验室,河北省石家庄市050091

出　　处：《中国组织工程研究》2016年第5期688-693,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(81073074;30472200);河北省自然科学基金资助项目(H2013206005);河北省高等学校科学技术研究重点项目(ZD2015053);河北省高等学校高层次人才科学研究项目(GCC2014013)~~

摘　　要：背景:近些年研究表明,鼻腔给药作为脑靶向给药的途径之一,可有效使通过其他给药途径不易透过血脑屏障的药物绕过血脑屏障,靶向递送到脑部,为治疗中枢神经系统疾病提供一种极有发展前景的给药途径。目的:研究大鼠鼻腔给药及静脉注射升麻苷H-1的药代动力学和脑靶向性归经的组织分布特性,探索升麻苷H-1利用鼻腔嗅觉区的鼻-脑通道进行鼻脑靶向给药的可行性。方法:鼻腔给药及静脉注射给予升麻苷H-1后,检测各时间点血浆和主要的归经组织器官(肺、脾、胃、大肠、肝、肾、脑、大脑、小脑、脑脊液、嗅球、嗅区等)药物浓度,绘制药-时曲线,用DAS程序拟合房室模型并计算药代动力学参数。结果与结论:1升麻苷H-1吸收迅速,分布广泛。在主要的归经器官中,肺、脑药物浓度分布均远高于其他脏器组织。2升麻苷H-1鼻腔给药后经以下吸收通路直接转运入脑:鼻腔嗅黏膜吸收进入蛛网膜下腔的嗅球,然后相继进入嗅区、脑脊液大脑、小脑等部位,嗅球是药物分子经鼻腔入脑的必经之路。3与静脉注射给药相比,升麻苷H-1鼻腔给药具有明显的肺、脑靶向性。BACKGROUND： Recent studies have suggested that intranasal administration is one of the ways to target drugdelivery, and can effectively make the drug that cannot pass through the blood brain barrier by other pathways to bypass the blood brain barrier, resulting in targeted delivery to the brain. It provides a promising route for the treatment of central nervous system diseases. OBJECTIVE： To study the pharmacokinetic and brain-targeted channel-tropism tissue distribution character of cimicifugoside H-1 after nasal and intravenous administration in plasma and tissues in rats, in order to evaluate the feasibility of developing brain-targeted nasal delivery system of cimicifugoside H-1 by the passage between nose and brain in nasal olfactory area. METHODS： After intravenous injection and nasal administration of cimicifugoside H-1, the drug concentrations of plasma and channel-tropism organs（lung, spleen, stomach, large intestine, liver, kidney, brain, brain, cerebellum, cerebrospinal fluid, olfactory bulb and olfactory region） were detected. Drug-time curve was drawn. DAS program was used to select apartment model and pharmacokinetics parameters. RESULTS AND CONCLUSION：（1） The pharmacokinetics characters of cimicifugoside H-1 are rapidly absorbed and extensively distribution. Among major channel-tropism organs, drug concentrations were higher in the lung and brain than in the other organs.（2） Cimicifugoside H-1 could be straightly transported into brain by the intranasal administration. The molecule through olfactory mucosa in nasal cavity entered into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, cerebrospinal fluid, cerebrum and cerebellum gradually. Olfactory bulb was the only way for drug molecule to go through nasal cavity into brain.（3） Compared with the intravenous injection, cimicifugoside H-1 through the intranasal administration has a significant channel-tropism of lung and brain targeting.

关 键 词：升麻属 投药 鼻内 药代动力学 组织工程 实验动物 心肺损伤与修复动物模型 升麻苷H-1 鼻腔给药 脑靶向归经 示踪剂 定量分布 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]