PLA-α-细辛脑纳米粒经鼻腔、静脉给药后药物动力学研究

Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles

采用乳化溶剂挥发法制备聚乳酸(PLA)-α-细辛脑纳米粒,并与静脉注射给药比较,研究PLA-α-细辛脑纳米粒鼻腔给药后药物的体内分布及脑组织的靶向性。结果显示:鼻腔给药和静脉注射后的脑靶向系数分别为1.65与1.16,PLA-α-细辛脑纳米粒鼻腔给药后的绝对生物利用度为74.2%,脑靶向效率为142.24%,鼻-脑传递百分比为29.83%。荧光标记法显示,PLA-α-细辛脑荧光纳米粒经鼻腔给药后,香豆素-6在脑组织中的荧光强度最大,达到脑靶向给药的目的;PLA-α-细辛脑荧光纳米粒静脉注射给药后,香豆素-6在肝组织中的荧光强度远高于鼻腔给药,表明PLA-α-细辛脑纳米粒经鼻腔给药可降低药物导致的肝毒性。此外,PLA-α-细辛脑荧光纳米粒经鼻腔给药后,香豆素-6在肺组织中的荧光强度较弱,解决了气流粉碎法制备的α-细辛脑干粉经鼻腔给药到达肺部量较多的缺点。体内研究表明:与静脉注射相比,PLA-α-细辛脑纳米粒鼻腔给药后的脑靶向性优于静脉注射。

PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respective- ly. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74. 2% , 142. 24 and 29. 83% , respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of eoumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nano- particles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanopartieles was much higher than that after intranasal administration, indicating that intranasal ad- ministration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxieity. In addition, the fluorescent intensity of cou- marin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asa- rune dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration.