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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。
Objective To prepare polylactic acid (NT-Ⅰ) polylactic acid (PLA) nanoparticles modified with methylated-polyethyleneglycol (Me-PEG) -PLA-NP and NT-I-NP) were used to investigate the pharmacokinetics of NT-I-NP rats after nasal administration. Methods Polyethylene glycol monomethyl ether polylactic acid copolymer (MePEG-PLA) was used as nanomaterial to prepare NT-Ⅰ-NP by double emulsion-solvent evaporation method. NT-Ⅰ-NP was injected into the caudal vein as a control group, and four groups of NT-Ⅰ-NP rats were administered intranasally. Brain microdialysis sampling was used to analyze the effect of NT-Ⅰ on periaqueductal gray, PAG) site concentration changes over time. Results NT-Ⅰ-NP with different particle size was round or round and uniform in size. The AUC (0-t) of NT-I-NP less than 100 nm after nasal administration in rats was 1.22, 1.34, 1.60 times (P <0.05) 100- 200, 200-300 and> , Indicating that the concentration of NT-I at the brain target site was significantly higher than that of other nanoparticles at the particle size of less than 100 nm. CONCLUSIONS: The particle size of nanoparticles has a significant effect on NT-I intracerebral delivery. NT-I-NP with a particle size of less than 100 nm can significantly increase the intracerebral concentration of NT-I. NP for protein peptide macromolecular drugs into the brain laid the foundation.