siRNA delivery by non lamella liquid crystal forming lipid containing liposomes

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15973
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Josai University
• Principal Investigator: Itakura Shoko 城西大学, 薬学部, 助教 (20787387)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: リポソーム / ドラッグデリバリーシステム / 外部刺激 / 温度応答性 / 癌治療

Outline of Final Research Achievements

As a drug delivery system (DDS) for cancer therapy, a strategy for achieving compatibility of in vivo stability and intracellular delivery is important. Development of nanoparticles such as lipid nanoparticle and liposomes has actively explored recently, and they are required to precisely control in vivo kinetics and intracellular kinetics of drug. In this study, the nanoparticles composed of a novel non-lamella liquid crystal forming lipid and conventional lamella forming lipid were constructed. The prepared formulations showed high intracellular delivery of the encapsulated drug, and these were thought to involve improved interactions with the cell membrane due to increased membrane fluidity caused by temperature changes. In addition, the tumor growth inhibition of tumor-bearing mice was observed by heating the tumor site with a 980 nm laser as an external stimulus.

Free Research Field

薬物送達学

Academic Significance and Societal Importance of the Research Achievements

本研究では、新規非ラメラ液晶形成脂質を組み込んだリポソームにより、腫瘍部位での外部刺激によって非ラメラ液晶形成脂質の高い生体膜との相互作用が発揮され、細胞内への薬物送達を向上することに成功した。全身投与によるナノ粒子製剤の薬物利用率は低いのが現状であるのに対して、外部刺激と組み合わせることで、腫瘍局所での薬物の利用が促進されることが期待される。この成果はsiRNAなど多様な創薬モダリティに対して、細胞内への導入までをコントロールすることでより高効率な癌治療のための薬物デリバリーシステムとして貢献できる。