摘要
目的:考察神经毒素(NT-1)纳米粒经大鼠鼻腔给药后的脑药物动力学特征。方法:采用125I同位素标记法,以清醒自由活动大鼠为实验模型,运用脑微透析取样技术,连续测定NT-1纳米粒和NT-1经大鼠鼻腔给药后右侧嗅球组织间液的放射性计数(min-1),再折算成相应的NT-1浓度,并利用药动学软件计算各个参数。结果:NT-1鼻腔给药后无法进入脑内,而NT-1纳米粒可进入脑内,其药动学符合开放性二室模型,tmax、cmax、AUC0→∞、t1/2(β)分别为(46.38±5.12)min、(3.98±0.51)ng/mL、(876.24±55.32)ng.min/mL和(132.45±24.26)h-1。结论:单纯NT-1鼻腔给药后无法进入脑内,而以纳米粒为载体,可显著增加其鼻腔吸收入脑,且能较快达到峰浓度,消除缓慢。
Aim： To investigate the brain pharmacokinetic profile of NT-1-loaded nanoparticles after intmnasal administration in rats. Mothods：Using microdialysis sampling technique in awake freely-moving rats, the counter per minute（cpm）of dialysates in fight olfactory bulb of NT-1-loaded nanoparticles and NT-1, radiolabeled with sodium ^125I- Iodide, were measured in a gamma-counter for radioactivity. After converting cpm into corresponding concentrations of NT-1 by in vivo recovery of microdialysis probes, the pharmacokinetic parameters were calculated. Results： No NT-1 in the brain could be detected after intranasal administration. However, the NT-1-loaded nanoparticles could be absorbed into the brain, and the pharmacokinetics accorded with the opening two-compartment model. The parameters tmax, Cmax, AUC0→∞, t1/2（β） were （46.38 ± 5.12） min, （3.98 ± 0.51 ） ng/mL, （876.24 ± 55.32） ng· min/mL and （132.45 ± 24.26） h^-1, respectively. Conelusion： NT-1 can not be delivered to the brain after intmnasal administration. Nevertheless, the absorption of NT-1 through nasal cavity into the brain may be significantly increased with the help of nanoparticles as carriers, and the time to maximal concentration was short, the elimination process was prolonged.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2007年第1期77-79,共3页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.30371781)~~
关键词
神经毒素
纳米粒
鼻腔给药
脑药物动力学
neurotoxin- 1 （NT- 1 ）
nanoparticles
intmnasal administration
brain pharmacokinetics
