2022 Fiscal Year Final Research Report
Development of a novel DDS capable of overcoming the blood-brain barrier by fusion of mesenchymal stem cell-derived exosomes and cerebral vessel-targeting liposomes for ischemic stroke therapy
| Project/Area Number |
21K18065
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 90120:Biomaterials-related
|
|---|
| Research Institution | Wakayama Medical University |
|---|
Principal Investigator |
Fukuta Tatsuya 和歌山県立医科大学, 薬学部, 講師 (90805160)
|
|---|
| Project Period (FY) |
2021-04-01 – 2023-03-31
|
| Keywords | 細胞外小胞 / エクソソーム / リポソーム / DDS / 脂質膜融合 / 高圧乳化処理 / マイクロフルイダイザー / がん |
|---|
| Outline of Final Research Achievements |
For the treatment of brain diseases (e.g., ischemic stroke), the way to overcome the blood-brain barrier (BBB) is necessary to realize efficient drug delivery to the brain. In this study, we focused on one of the extracellular vesicles, exosomes (Exos), as Exos derived from some kinds of cells were reported to have the capability to pass through the BBB and deliver entrapped functional molecules. At first, we attempted to prepare functional nanoparticles by membrane fusion of Exos, on which membranes phosphatidylserine (PS) is reported to be present, and liposomes composed of PS. The prepared nanoparticles exhibited high cellular uptake into cancer cells and brain endothelial cells in vitro. Also, the present study demonstrated that use of high-pressure homogenization (HPH) using a microfluidizer is a promising approach to modify Exos with functional lipids and also to encapsulate low-molecular drugs into Exos, and that the prepared functional Exos is useful for cancer therapy.
|
| Free Research Field |
薬剤学・DDS
|
| Academic Significance and Societal Importance of the Research Achievements |
細胞外小胞エクソソーム（Exo）は、BBB透過性を有するなどの利点から、薬物送達システム（DDS）への利用が期待されており、リポソーム等のナノ粒子へのExo様機能の付与やExoへの簡便な機能性分子の修飾や高効率薬物封入の実現は、Exoを用いたDDS製剤の開発研究を加速化する新たな技術となる点で学術的意義がある。また、中枢疾患は未だアンメットメディカルニーズが多いが、本研究のさらなる発展は、中枢創薬に資する新たなDDS技術の開発に貢献できる可能性がある点で、社会的意義があると言える。
|
