Development of bone-targeting, thermal-sensitive micelles for treatment of CKD-MBD

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23812
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Doshisha Women's College of Liberal Arts
• Principal Investigator: Yamsahita Shugo 同志社女子大学, 薬学部, 助教 (30845730)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: DDS / ポリペプチドミセル / 熱応答性 / CKD-MBD / FGF23

Outline of Final Research Achievements

Kidney fibrosis initiated by chronic kidney disease-mineral and bone disorder (CKD-MBD) is induced by fibrosis growth factor 23 (FGF23) secreted from the bone. However, inhibition methods of kidney fibrosis correlated CKD-MBD have not been established. In this study, we developed the kidney fibrosis therapy method by using the diblock copolypeptide between poly aspartic acid and aspartic acid/phenylalanine irregular polymer (DDF). Accumulation rate of GW0742 which is FGF23 inhibitor, encapsulated DDF (GW-DDF) was 3.5-fold higher than GW0742 only after intravenous injection in mice. In addition, FGF23 blood level was suppressed approximately 1/7 compared with untreated CKD model mice by intravenous injection of GW-DDF. These findings indicate that DDF is a promising bone-targeting polypeptide micelle for the delivery of GW0742 and suppressing of FGF23 secretion in bone.

Free Research Field

薬剤学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた成果は、新たな国民病と言われる慢性腎臓病を起因とした CKD-MBD などの骨関連疾患治療を目的とした医薬品開発に対して、手がかりとなる基礎的情報を提供できると考える。特に (1) ヒトの体を形作るアミノ酸のみで構成された骨指向性薬物キャリア (DDF) 開発に成功したこと (2) DDF が熱応答性を有しており骨組織での薬物放出を外部から制御できる可能性を見出したこと (3) 線維芽細胞成長因子 23 などの骨から分泌される病態因子の分泌抑制方法を見出したことにより、骨関連疾患の治療戦略の幅を広げることで、将来的な健康寿命の延伸に貢献する一助となり得ると考える。