Analysis for brain transfer of water-soluble macromolecule administered by intranasal formulation consisting of IL encapsulated porous silica

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16059
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Nihon University
• Principal Investigator: SUZUKI Naoto 日本大学, 薬学部, 講師 (60756005)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: イオン液体 / 経鼻投与 / 鼻腔内滞留性 / 多孔性シリカ / 水溶性中分子 / NSAIDs / 粘膜透過性 / 噴霧性

Outline of Final Research Achievements

In this study, we applied ionic liquids that can enhance mucosal permeability to etodolac (BBB-impermeable drug) and inulin (water-soluble middle molecule) and administered them into the nasal cavity, where the direct nasal-to-brain pathway exists, and found that the transfer of these compounds into the olfactory bulb, brain and blood was increased. These results suggest that ionic liquids are useful materials for the design of intranasal formulations targeting the brain.
Since the ionic liquid is viscous and difficult to be sprayed with a general nasal device, the ionic liquid was encapsulated in porous silica, which is an absorbent, under optimal conditions. As a result, it was possible to design an ionic liquid-containing powder nasal administration formulation that exhibited excellent flowability and could be sprayed with a general nasal device.

Free Research Field

製剤学，薬剤学，DDS

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会への突入により増加傾向にある難治性中枢性疾患の治療薬に対するニ－ズは増加の一途である．本研究では，経鼻投与した薬物の脳移行性に及ぼす影響とその製剤化技術ならびに性能を明らかにしたことで，これら疾患に対する治療薬の開発を促進する一助となることが期待される．また，脳移行性の乏しさから開発を断念した化合物や，市販された脳標的医薬品のリポジショニングするための製剤設計にも貢献し得る知見であると考えられた．