Shi Senlin, Wu Jinjin, Dai Wenyun, Li Changyu, Ge Weihong
College of Pharmaceutical Science, Zhefiang Chinese Medical University, Hangzhou 310053, China.
Zhongguo Zhong Yao Za Zhi. 2010 Sep;35(18):2453-6.
To evaluate the feasibility of developing brain-targeted nasal delivery system of scutellarin by the passage between nase and brain in nasal olfactory area.
The samples of cerebrospinal fluid (CSF) and blood were prepared by cranial puncture and femoral artery catheterization methods respectively according to the certain sampling time after drug administered. The scuteIlarin concentration of samples were determined by 125 marked method. Pharmacokinetic parameters were calculated by trapezoidal rule. The brain-targeted trendence were evaluated by the value of the index AUC(brain)/AUC(plasma).
The distribution of scutellarin in brain following intranasal administration was different between tissues. Drug concentration in olfactory bulb achieved to peak at 5-15 min after intranasal administration, while in brain tissue was 30-60 min. Above all, peak concentration in olfactory bulb and olfactory region respectively were (574.8 +/- 205.), (323.4 +/- 128.3) ng x g(-10, both are higher than CSF, which is (123.2 +/- 29.3) ng x g(-1). Moreover, the distribution of scutellarin given by intranasally in brain was: olfactory bulb (OB) >> olfactory region (OR) > cerebrospinal fluid (CSF) > cerebellum(CB) > medulla oblongata (MO) > cerebrum (CR); AUC(0-240) of olfactory bulb, olfactory region and CSF after scutellarin intranasal administration were 5.54, 5.07 and 5.51 times of that after intravenous injection, respectively. And the AUC(0-240) of other brain tissues after intranasal administration were also higher than that after intravenous injection. AUC(brain tissue)/ AUC(plasma) of every brain tissues by intranasally are all higher than that by intravenously remarkably. For instance, 5 min after intranasal administration, the value of AUC(CSF)/ AUC(plasma), AUC(OB)/AUC(plasma), and AUC(CR)/AUC(plasma) were 30.34, 56.93, and 6.14 times of that by intravenously.
Part of scutellarin could be straightly transported into brain by the intranasal administration. Its absorption pathway was: the molecule of Scutellarin throughed olfactory mucosa in nasal cavity into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, CSF, cerebrum and cerebellum gradually. It showed that olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. It had a significant trendence of brain-targeted when compared to oral administration and intravenous injection, which indicated a certain feasibility to develop a brain-targeted nasal delivery system for scutellarin.
通过鼻腔嗅区鼻脑通路开发灯盏花素脑靶向鼻腔给药系统，评估其可行性。
给药后按一定采样时间分别采用颅穿刺和股动脉插管方法制备脑脊液（CSF）和血液样本。采用125标记法测定样本中灯盏花素浓度。用梯形法则计算药代动力学参数。通过AUC（脑）/AUC（血浆）值评估脑靶向趋势。
鼻腔给药后灯盏花素在脑内各组织的分布存在差异。鼻腔给药后5 - 15分钟嗅球药物浓度达峰，而脑组织为30 - 60分钟。嗅球和嗅区的峰浓度分别为（574.8±205.）、（323.4±128.3）ng·g⁻¹，均高于脑脊液的（123.2±29.3）ng·g⁻¹。此外，鼻腔给药灯盏花素在脑内的分布为：嗅球（OB）>>嗅区（OR）>脑脊液（CSF）>小脑（CB）>延髓（MO）>大脑（CR）；灯盏花素鼻腔给药后嗅球、嗅区和脑脊液的AUC（0 - 240）分别是静脉注射后的5.54、5.07和5.51倍。鼻腔给药后其他脑组织的AUC（0 - 240）也高于静脉注射。鼻腔给药各脑组织的AUC（脑组织）/AUC（血浆）均显著高于静脉给药。例如，鼻腔给药5分钟后，AUC（CSF）/AUC（血浆）、AUC（OB）/AUC（血浆）和AUC（CR）/AUC（血浆）的值分别是静脉给药的30.34、56.93和6.14倍。
灯盏花素经鼻腔给药部分可直接入脑。其吸收途径为：灯盏花素分子经鼻腔嗅黏膜进入蛛网膜下腔的嗅球，进而逐渐进入嗅区、脑脊液、大脑和小脑。表明嗅球是药物分子经鼻腔入脑的唯一途径。与口服给药和静脉注射相比，具有显著的脑靶向趋势，提示开发灯盏花素脑靶向鼻腔给药系统具有一定可行性。
