聚山梨酯80修饰的神经毒素纳米粒鼻腔给药镇痛作用及体内分布的研究

Antinociceptive Properties of Nasal Delivery of Neurotoxin-loaded Nanoparticles Coated with Polysorbate-80 and Brain Targeting Efficiency in Mice of P-80-NT-NP

[目的]考察聚山梨酯80(polysorbate-80,P-80)修饰及鼻腔给药对神经毒素纳米粒(neurotoxin-nanoparticles,NT-NP)镇痛作用及体内分布的影响。[方法]制备P-80修饰的神经毒素纳米粒(P-80-NT-NP),通过不同给药途径,利用小鼠热板法和甲醛致痛法评价其中枢镇痛作用,并将其与NT-NP和神经毒素(neurotoxin,NT)进行比较;通过小动物活体成像技术研究P-80修饰及未修饰的NT-NP鼻腔给药后的体内分布情况。[结果]热板法实验结果显示P-80-NT-NP经鼻腔给药后在90min达到药效高峰,痛阈提高率为69.92%,镇痛效果明显强于NT-NP鼻腔给药组(P<0.05)以及NT腹腔(痛阈提高率63.97%)和肌肉注射组(痛阈提高率63.44%),且在甲醛致痛试验中P-80-NT-NP经鼻腔给药后在第1时相和第2时相均能明显抑制小鼠的疼痛反应(P<0.01),且与小动物成像结果一致,显示NT-NP经P-80修饰后其中枢镇痛效果明显强于未修饰的NT-NP且鼻腔给药均优于其他给药途径,药效持续时间长且入脑迅速。[结论]NT-NP经P-80修饰后,鼻腔给药有利于药物入脑,脑内药物浓度增加,明显提高镇痛效果。

[Objective] To study coating polysorbate-80 and delivering in nasal how to influence antinociceptive properties and their distribution property in mice of Neurotoxin. [Methods] To prepare the Neurotoxin-loaded nanoparticles coated with polysorbate-80, explore the analgesia effect of different administration pathways of P-80-NT-NP and compare the analgesia with NT-NP and NP. The hot plate method and the formalin test were used to evaluate the effect. Different distributions between P-80-NT-NP and NT-NP in mice were evaluated by in vivo imaging system.[Result] The results of pharmaco-dynamics experiment showed after intranasal administration of P-80-NT-NP in 90 min the efficacy reached the peak, the pain threshold was69.92%, the analgesic effect was obviously better than the group of NT-NP in.（P〈0.05） and the group of NT ip.（the pain threshold was 63.97%） and NT im.（the pain threshold was 63.44%）; the formalin test results showed that after intranasal administration of P-80-NT-NP, mice were all inhibited significantly of lickingin in the phase 1 and phase 2, the results were similar in vivo imaging. It showed that the nasal administration of Neurotoxin-loaded nanoparticles with the help of polysorbate-80 had the best analgesia effect. [Conclusion] After the neurotoxin nanoparticles coated with polysorbate-80, it became simpler to cross the BBB, the concentration of drug in brain increased, the effect of analgesia significantly improved.