Comprehensive investigations on development, biodistribution, and safety of nanoparticle-loaded dry powder formulations for inhalation with high nanoparticle redispersibility and aerosol performance

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08258
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Meijo University
• Principal Investigator: Okuda Tomoyuki 名城大学, 薬学部, 准教授 (20513857)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ナノ粒子 / 吸入粉末剤 / 再分散 / 粉末微粒子設計 / エアロゾルデリバリー / 噴霧急速凍結乾燥法

Outline of Final Research Achievements

In the present study, effective excipients and powderization techniques were comprehensively investigated for successful development of nanoparticle-loaded dry powder formulations for inhalation with high nanoparticle redispersibility and aerosol performance, demonstrating the superiority of combination of trehalose and leucine through spray-freeze drying. Moreover, surface modification of nanoparticles with functional groups or polyethylene glycol could significantly improve their redispersibility, whereas their particle size did not affect it. Pharmacokinetic studies in vitro and in vivo showed that distribution or membrane association and permeation of nanoparticles in the lungs after inhalation can be affected by their redispersion and local, highly concentrated exposure in dry powder formulations besides their surface modification and particle size, resulting in their different pharmacokinetics between dry powder and dispersion formulations.

Free Research Field

薬物送達学、製剤学、薬剤学

Academic Significance and Societal Importance of the Research Achievements

リポソームなどの医療用ナノ粒子を応用することで、徐放性あるいは滞留性などのドラッグデリバリー機能を付与した新たな吸入粉末剤の開発が強く望まれている。本研究で得られた知見は、このような製剤を効率的に開発するための極めて有用な情報源となる。特に、吸入粉末製剤化に伴うナノ粒子の再分散が及ぼす肺内動態への影響を動物実験で実証したのは、本研究が初めてと思われる。吸入粉末製剤化は、ナノ粒子とともに生体内安定性に乏しい医薬品候補の臨床応用を実現する方略として有望であり、難治性・致死性の肺疾患に対する画期的な治療法の確立に大きく貢献するものと考えられる。