陆瑾+郭立玮+付廷明+朱国龙+戴真南+展冠军+陈丽丽

[摘要] 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。

[关键词] PLA-α-细辛脑纳米粒； 鼻腔； 药物动力学； 脑靶向

[Abstract] 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 respectively. 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 coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles， achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration， indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition， the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration， which solved the shortcomings of intranasal administration of α-asarone 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.

[Key words] PLA-α-asarone nanoparticles； intranasal； pharmacokinetic； brain targeting

α-細辛脑是天南星科植物石菖蒲Acorus tatarinowii Schott的主要活性成分之一，研究报道：α-细辛脑通过作用于NO水平治疗阿尔茨海默病[1]，通过抑制海马神经元的活性及γ-氨基丁酸（GABA）受体的表达[2]治疗癫痫，同时其可透过血脑屏障。因此，α-细辛脑具有治疗中枢性神经系统疾病的前景。目前，α-细辛脑主要有2种给药方式，以胶囊剂或片剂的形式给药，生物利用度分别仅有2.73%，5.56%[3]；若采用静脉注射给药，由于α-细辛脑较高的脂溶性使其在制备过程中加入了吐温、丙二醇等助溶剂，而吐温、丙二醇等助溶剂又是导致细辛脑注射液过敏性休克等严重不良反应的重要原因之一[4-5]。……