石杉碱甲二元醇质体温敏凝胶大鼠鼻腔给药药动学及脑靶向性研究

Pharmacokinetics and brain targeting of thermosensitive gel binary ethosomes of huperzine A via nasal administration in rats

目的研究石杉碱甲二元醇质体温敏凝胶大鼠鼻腔给药药动学及脑靶向性。方法 UPLC-MS/MS法测定大鼠血浆及脑组织中石杉碱甲含量,计算主要药动学参数及脑靶向评价参数。结果与温敏凝胶鼻腔给药及石杉碱甲注射剂静脉给药比较,二元醇质体温敏凝胶鼻腔给药大鼠脑组织AUC_(0~)_(t)升高(P<0.01),MRT_(0~)_(t)延长(P<0.05),大鼠血浆C_(max)明显变化(P<0.01),DTE、DTP分别为133.58%、25.14%,与温敏凝胶相比分别提高24.45%、16.77%。结论石杉碱甲二元醇质体温敏凝胶鼻腔给药具有脑靶向性,可增加药物在脑组织中的分布。

AIM To study the pharmacokinetics and brain targeting of thermosensitive gel binary ethosomes of huperzine A via nasal administration in rats.METHODS UPLC-MS/MS was adopted in the content determination of huperzine A in rat plasma and brain tissue,and main pharmacokinetic parameters and target evaluation parameters were calculated.RESULTS Compared with nasal administration of thermosensitive gel and intravenous administration of huperzine A injection,nasal administration of thermosensitive gel binary ethosomes demonstrated increased AUC_(0-)_(t)(P<0.01) and prolonged MRT_(0-)_(t)(P<0.05) in rat brain tissue,and obvious change in C_(max) in rat plasma(P<0.01),whose DTE and DTP were 133.58% and 25.14%,which were 24.45% and 16.77% higher than those of thermosensitive gel,respectively.CONCLUSION The nasal administration of thermosensitive gel binary ethosomes of huperzine A displays brain targeting,which can enhance the distribution of drugs in brain tissue.