Development of bone-responsive drug delivery system for the therapy of osteoporosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K20698
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Keio University
• Principal Investigator: Fukui Yuuka 慶應義塾大学, 理工学部(矢上), 講師 (50635836)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: リポソーム / ナノカプセル / ドラッグデリバリーシステム / 骨粗鬆症

Outline of Final Research Achievements

In recent years, the number of people who suffer from osteoporosis are increasing with the shift to an aging society and change in people’s lifestyles. In this study, we developed therapeutic materials for osteoporosis. First, we produced a nanocapsule via deposition of biopolymers on the surface of liposome. The polymer wall was constructed with an inner layer with cell penetration activity and an outer layer with bone-targeting ability. The enzymatic degradation of the outer layer in response to the acidic environment provided by osteoclasts led to the surface display of inner layer. In addition, enzymatic degradation of the polymer wall facilitated the release of cargo. Therefore, it is expected that the nanocapsule will deliver drugs to osteoclasts to reduce bone resorption. Next, calcium phosphate, which is the main constituent of bone, was produced inside the liposome. We expect that delivery of nanosized calcium phosphate to bone tissue will promote the bone formation.

Free Research Field

高分子化学

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症の治療薬の中でもビスホスホネート製剤が、最も多く使用されている。一方、骨と強固に結合し、長期に渡って骨組織に残留するため、骨代謝回転を過度に抑制して、骨強度の低下による骨折、顎骨壊死などの重篤な副作用を引き起こすといわれている。本方法は、カプセルの体内動態制御(骨標的指向性)に加えて、細胞内動態制御(破骨細胞内での薬剤放出)を実現することで、薬剤を破骨細胞にだけ作用させることが可能となり、副作用の低減が期待できる。さらに、カプセルを用いて骨形成素材をデリバリーし、骨形成を誘発することによって、骨粗鬆症の予防、進行の遅延、早期治療効果の発現が期待できる。