中文摘要：

目的制备不同粒径甲基化聚乙二醇（methylated-polyethyleneglycol,Me-PEG）修饰的神经毒素-Ⅰ（neurotoxin,NT-Ⅰ）聚乳酸（polylactic acid,PLA）纳米粒（NT-Ⅰ-MePEG-PLA-NP,NT-Ⅰ-NP）,并考察不同粒径NT-Ⅰ-NP大鼠鼻腔给药后脑药动学特征。方法以聚乙二醇单甲醚聚乳酸共聚物（MePEG-PLA）为纳米材料,采用复乳-溶剂挥发法制备NT-Ⅰ-NP。以尾静脉注射NT-Ⅰ-NP为对照组,4组不同粒径NT-Ⅰ-NP大鼠鼻腔给药,运用脑微透析取样技术分析NT-Ⅰ在大鼠中脑导水管周围灰质（periaqueductal gray,PAG）部位浓度的经时变化。结果不同粒径的NT-Ⅰ-NP呈圆形或类圆形,大小均匀。大鼠鼻腔给药后小于100nm的NT-Ⅰ-NP的AUC（0-t）分别是100～200、200～300和大于300nm NT-Ⅰ-NP的1.22、1.34、1.60倍（P〈0.05）,表明粒径小于100nm时NT-Ⅰ在脑靶部位的浓度明显高于其他粒径的纳米粒。结论纳米粒的粒径对NT-Ⅰ的脑内递送有着较为明显的影响,粒径小于100nm的NT-Ⅰ-NP可以明显增加NT-Ⅰ的脑内浓度,这一结果为研究适宜粒径的NP用于蛋白多肽类大分子药物入脑奠定了基础。

英文摘要：

Aim To prepare NT-Ⅰ loaded nanoparticles with different diameters modified by Methylated-polyethyleneglycol （Me-PEG） and evaluate their brain pharmacokinetics after administered nasally in rats. Methods NT-Ⅰ-NP was prepared by emulsion/solvent evaporation method and MePEG-PLA was used as the carrier material. Microdialysis technique and fluorospectrophotometry were used to determine NT-Ⅰ concentration after nasal administration in the brain of rats. Results The appearance of all NT-Ⅰ-NP groups was round or similar. The AUC（0-t） of below 100 nm NT-Ⅰ-NP was 1.22 fold as that of 100~200 nm NT-Ⅰ-NP,1.34 fold as that of 200~300 nm and 1.60 fold as that of exceed 300 nm NT-Ⅰ-NP（P0.05） treated nasal administration in rats. The quantity and speed of below 100 nm NT-Ⅰ-NP was remarkably higher than the other three size NT-Ⅰ-NP. Conclusions The size of NP has some significant influence on drug delivery to the brain. When the diameter is below 100 nm,the NT-Ⅰ-NP significantly improves the NT-Ⅰ concentration level in brain. The outcomes of this research provide a feasible path to develop suitable diameter NP for the administration of giant molecule drug such as protein and polypeptide.