神经毒素纳米粒大鼠鼻腔给药的脑药物动力学研究  

Brain pharmacokinetics of NT-1-loaded nanoparticles after intranasal administration in rats

作　　者：程巧鸳[1] 李范珠[1] 

机构地区：[1]浙江中医药大学药学院,杭州310053

出　　处：《中国药科大学学报》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)~~

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.

关 键 词：神经毒素 纳米粒 鼻腔给药 脑药物动力学 

分 类 号：R965[医药卫生—药理学]