摘要
目的考察3种吸收促进剂对于多肽类大分子物质神经毒素(NT-Ⅰ)鼻腔给药后脑内递药的作用。方法运用125I-NT-Ⅰ同位素标记法,以清醒大鼠为实验模型,采用同步多处脑微透析技术,连续测定单用NT-Ⅰ(105μg·kg-1)以及NT-Ⅰ合用冰片、薄荷和冰片/薄荷低共熔物大鼠鼻腔给药后分别在嗅球和小脑组织间液中NT-Ⅰ的浓度。结果单用NT-Ⅰ鼻腔给药进入脑内非常有限。冰片/薄荷低共熔物组小脑和嗅球中AUC分别是(2283.51±34.54)和(1358.58±32.56)ng.min.mL-1,均低于单用冰片或薄荷组中在同一脑区的AUC。而两个脑区中低共熔组的达峰时间均较单独使用冰片和薄荷脑组的达峰时间短(P<0.05)。结论冰片、薄荷和冰片/薄荷低共熔物均有促进NT-Ⅰ通过鼻黏膜吸收入脑的作用。冰片/薄荷脑低共熔物吸收促进作用较单独冰片和薄荷脑弱。但是,冰片/薄荷脑低共熔物可促进NT-Ⅰ鼻腔给药后快速入脑。
OBJECTIVE To investigate the contribution of three absorption enhancers to delivery of the centrally active polypeptide cobrotoxin （NT-Ⅰ） after intranasal （i.n.） administration to the brain. METHODS The NT-Ⅰ profiles in the brain were studied using dual-probe microdialysis in conscines free-moving rats. NT-Ⅰ,radiolabeled with sodium 125I-Iodide （125I-NT-Ⅰ）,was administered at the dose of 105 μg·kg-1 intranasally in rats （n=20） with and without borneol,menthol and borneol/menthol eutectic mixture （＋BMEM） as absorption enhancers,respectively. The dialysates sampled simultaneously from right olfactory bulb and cerebellar nuclei were measured with a gamma-counter for radioactivity,and the concentration of NT-Ⅰwas recalculated by in vivo recovery of microdialysis probes. RESULTS The delivery of NT-Ⅰafter i.n. administration without absorption enhancer was significantly limited. The area under the curve （AUC） in cerebellar nuclei （2 283.51±34.54） ng·min·mL-1 and olfactory bulb （1 358.58±32.56）ng·min·mL-1 following i.n. application （＋BMEM） was not significantly different from those with borneol and menthol alone. Following i.n. application,the time to peak concentration（＋BMEM） in cerebellar nuclei （85 min）,was statistically longer than that in olfactory bulb（75 min ）. CONCLUSION Three absorption enhancers all can enhance brain transport of NT-Ⅰafter i.n. administration with non-even distribution in discrete regions of rat brains. Compared with borneol and menthol alone,BMEM improved brain delivery of NT-Ⅰ intranasally administered rapidly.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2010年第13期1011-1015,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助项目(30371781)
关键词
神经毒素
微透析
低共熔物
鼻腔给药
鼻脑通路
neurotoxin
microdialysis
eutectic mixture
intranasal administration
nasal-brain passway
