目的制备聚山梨酯80包裹的神经毒素-Ⅰ（NT-Ⅰ）聚氰基丙烯酸正丁酯（PBCA）纳米粒（T-80-NT-Ⅰ-PBCA-NP）,并考察其脑内药动学特征。方法以PBCA为纳米材料,采用乳化聚合法制备T-80-NT-Ⅰ-PBCA-NP,以大鼠为实验对象,经鼻腔给药后,运用脑微透析取样技术,以未包裹的NT-ⅠPBCA纳米粒（NT-Ⅰ-PBCANP）为对照组,研究神经毒素-Ⅰ在脑内中脑导水管周围灰质（PAG）的动力学过程。结果大鼠鼻腔给药后,聚山梨酯-80包裹与未包裹的NT-ⅠPBCA纳米粒药物浓度-时间曲线符合开放性二室模型,其主要药动学参数t_max分别为（71.018±7.641）、（55.830±6.072） min;C_max分别为（117.189±10.036）、（52.277±6.217） ng/mL;AUC_0→∞分别为（22 836.633±51.052）、（12 786.934±30.723） ng·min·mL^-1。结论T-80-NT-Ⅰ-PBCA-NP鼻腔给药后延长NT-Ⅰ达峰时间,且显著提高NT-Ⅰ的脑内浓度。

ObjectiveTo prepare neurotoxin-I(NT-I)polybutylcyanoacrylate (PBCA) nanoparticles(NP) coated by polysorbate-80 and conduct its pharmacokinetic study in brain after intranasal administration in rats.MethodsNT-I Nanoparticles were prepared by emulsion polymerization method with PBCA as nanoparticle material. The pharmacokinetics in brain of NT-I nanoparticles coated or uncoated by polysorbate-80 after nasal application was characterized using brain microdialysis sampling technique.Results The concentration-time curve of NT-I nanoparticles coated and uncoated polysorbate-80 after intranasal administration in rats accorded with the two-compartment model. The pharmacokinetic parameters of t_max were (71. 018±7.641) and (55. 830±6. 072) min; C_max were(117.189±10.036 ) and(52.277±6.217 )ng/mL, and AUC_0→∞ were (22 836. 633±51.052) and (12786.934±30.723 )ng·min·mL^-1，respectively.ConclusionPolysorbate-80 coating of PBCA nanoparticles could extend the time to peak of NT-I administered intranasally and significantly improve the NI-I concentration level in brain.

国家自然科学基金项目(30772793,30371781);浙江省卫生高层次创新人才培养工程