PEG-PLA-α-细辛脑纳米粒经鼻腔、静脉给药后的药动学研究

Pharmacokinetics of PEG-PLA-α-asarone Nanoparticles After Nasal and Intravenous Administration

关键词:  PEG-PLA-α-细辛脑纳米粒  鼻腔给药  药动学  脑靶向

Key words:  PEG-PLA-α-asarone nanoparticles  intranasal  pharmacokinetic  brain target

摘要:

目的 采用与静脉注射对比的方式，研究聚乙二醇-聚乳酸-α-细辛脑纳米粒（PEG-PLA-α-细辛脑纳米粒）鼻腔给药后在大鼠体内的药物动力学。方法 以大鼠为动物模型，采用血药动力学、脑药动力学及荧光标记法对比研究PEG-PLA-α-细辛脑纳米粒经鼻腔给药与静脉注射后药物/纳米粒在大鼠体内的分布情况。结果 PEG-PLA-α-细辛脑纳米粒静脉注射及鼻腔给药后血浆中的AUC_（0-∞）分别为（11032.4±1 827.1）ng·mL^-1·min及（5 992.9±717.5）ng·mL^-1·min，C_max分别为（421.9±100.2）ng·mL^-1及（171.7±26.3）ng·mL^-1，PEG-PLA-α-细辛脑纳米粒鼻腔给药后的绝对生物利用度F为54.3%。PEG-PLA-α-细辛脑纳米粒静脉注射后α-细辛脑在脑组织中的C_max与鼻腔给药后α-细辛脑在脑组织中的浓度C_max分别为（217.9±29.9）ng·mL^-1及（334.2±62.7）ng·mL^-1，PEG-PLA-α-细辛脑纳米粒静脉注射与鼻腔给药后的AUC_brain/AUC_plasma值分别为1.37和2.85，且两者具有统计学意义。PEG-PLA-α-细辛脑纳米粒鼻腔给药后的药物脑靶向效率及鼻-脑传递百分比分别为208.03%及52.01%。荧光标记法结果显示，PEG-PLA-α-细辛脑纳米粒鼻腔给药后脑靶向性比静脉注射后更强。结论 PEG-PLA-α-细辛脑纳米粒适合于鼻腔给药治疗脑部疾病。

Abstract:

OBJECTIVE To study the pharmacokinetics of polyethylene glycol-polylactic acid-α-asarone nanoparticles (PEG-PLA-α-asarone nanoparticles) after nasal administration compared with intravenous administration in rats. METHODS The rats were used as model. The pharmacokinetics, brain pharmacokinetics and fluorescent labeling method were used to study the distribution of PEG-PLA-α-asarone nanoparticles after nasal administration compared with intravenous administration in rats. RESULTS The results showed that the AUC_(0-∞) in plasma after intravenous and nasal administrations of PEG-PLA-α-asarone nanoparticles were (11 032.4±1 827.1)ng·mL^-1·min and (5 992.9±717.5) ng·mL^-1·min, C_max were (421.9±100.2)ng·mL^-1 and (171.7±26.3)ng·mL^-1, respectively. The absolute bioavailability F was 54.3% after nasal administration of PEG-PLA-α-asarone nanoparticles. The C_max of α-asarone in brain tissue after intravenous and nasal administrations of PEG-PLA-α-asarone nanoparticles were (217.9±29.9)ng·mL^-1 and (334.2±62.7)ng·mL^-1. The values of AUC_brain/AUC_plasma on PEG-PLA-α-asarone nanoparticles after intravenous and nasal administrations were 1.37 and 2.85, respectively. It had statistically significant. The drug brain targeting efficiency and nasal-brain transmission percentage of PEG-PLA-α-asarone nanoparticles after nasal administration were 208.03% and 52.01%, respectively. The result of fluorescent labeling showed that PEG-PLA-α-asarone nanoparticles had stronger brain targeting after nasal administration. CONCLUSION PEG-PLA-α-asarone nanoparticles are suitable for nasal administration for the treatment of brain diseases.