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冰片-薄荷脑低共熔物对纳米粒鼻腔给药载药入脑的影响.doc

冰片-薄荷脑低共熔物对纳米粒鼻腔给药载药入脑的影响.doc

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冰片-薄荷脑低共熔物对纳米粒鼻腔给药载药入脑的影响( 柴国宝(,夏爱晓,蔡鑫君,魏颖慧,冯健,李范珠( (浙江中医药大学药学院,杭州,310053) 摘要 目的:考察中药冰片-薄荷脑低共熔物对神经毒素纳米粒鼻腔给药吸收入脑的影响。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,测定脑内神经毒素浓度的变化,并应用药动学软件计算药动学参数。结果:中药冰片-薄荷脑低共熔物纳米粒脑药动学符合二室模型,Tmax、Cmax、AUC、t1/2(β)分别为0.68h、27.32ng/mL、132.68 ng·h/mL、3.1076h,其入脑的速度与程度均优于单用薄荷脑或者冰片。结论:神经毒素纳米粒在冰片-薄荷脑低共熔物作用下,可显著增加其鼻腔吸收入脑的药量,且能较快达到峰浓度,消除缓慢。 关键词:冰片-薄荷脑低共熔物;纳米粒;鼻腔给药;脑药动学 Effect of borneol/mentholum eutectic mixture on nasal-brain delivery of neurotoxin loaded nanoparticles CHAI Guo-bao, XIA Ai-xiao, CAI Xin-jun,WEI Ying-hui, Fen Jian,LI Fan-zhu* (College of Pharmacy, Zhejiang University of Traditional Chinese Medicine ,Hangzhou,310053) ABSTRACT Objective To investigate the absorption enhancen effect of borneol/mentholum eutectic mixture (BO/ME) on nasal-brain delivery of neurotoxin loaded nanoparticles . Methods Using microdialysis sampling technique in awake freely- moving rats , the counter per minute (cpm) of dialysates in right PAG of NT-loaded nanoparticles with the BO/ME (BO/ME-NT-NP), radiolabeled with sodium125I-Iodide, were measured in a gamma-counter for radioactivity. After converting cpm into corresponding concentrations of NT byin vivorecovery of microdialysis probes, the pharmacokinetic parameters were calculated. Results The BO/ME-NT-NP could be absorbed into the brain, much better to NT-NP and the nanoparticles with borneol or mentholum only, and the pharmacokinetics accorded with the two-compartment model. The parameters tmax, cmax, AUC, t1/2 (β) were 0.68h, 27.32ng/mL, 132.68 ng·h/mL, 3.1076h. Conclusion With adding BO/ME as absorption enhancer, NT could be significantly increased in the brain with the help of nanopartilces as carriers, and the time to maximal concentration was short, the elimination process was prolonged. Key Words: bornel/mentholum eutectic mixture; nanoparticles; intranasal administer- ation; brain pharmacokinetic 纳米药物载体系统具有靶向、缓释、保护药物等多重作用。前期实验表明[1-2]:纳米粒作为神经毒素(Neurotoxin,NT)的载体,既能保持药物的活性,又能增加药物的脑内含量。临床上,NT主要的给药方式

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