The study on the brain uptake of oxytocin after intranasal administration -The effect of cerebrospinal fluid circulation-

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16098
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Tanaka Akiko 神戸薬科大学, 薬学部, 講師 (30824320)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 鼻腔内投与 / 脳内送達 / Glymphatic system / oxytocin / 自閉症治療

Outline of Final Research Achievements

The purpose of this study was to develop DDS formulations that improves the efficiency of brain delivery after intranasal administration of oxytocin (OXT) by controlling the flow of extracellular fluid (Glymphatic System, GPsys). Intranasal administration of OXT and acetazolamide (AZA), which has been reported as an AQP4 inhibitor, showed that the ratio of brain AUC to blood AUC of OXT was higher than that after administration of OXT alone. In addition, changes in the expression level of AQP4 and a decrease in the amount of cerebrospinal fluid (CSF) were observed by AZA administration, suggesting that AZA may affect the flow of CSF. These results suggest that GPsys may have a significant impact on the delivery of OXT in the brain.

Free Research Field

生物薬剤学、薬物動態学

Academic Significance and Societal Importance of the Research Achievements

脳細胞外液の流れであるGlymphatic System (GPsys) が提唱され、薬物の脳移行経路にはGPsysの関与の可能性が指摘されているが、その影響は評価されていないのが現状である。本研究は、その情報を基盤とする鼻腔内投与型DDS開発を目的とし、OXTによる自閉症スペクトラム障害 (ASD) 治療に対して、画期的な治療システムを提唱できる可能性が高い。また、本研究はASD治療法の開発にとどまらず、アルツハイマー病、パーキンソン病などの神経変性疾患などの脳疾患を対象としたペプチド・タンパク性医薬品による新規治療法の開発に大きく貢献できるものと考える。