Establishment of a Pharmacokinetics-Pharmacodynamics modeling evaluation system to enable function vs. efficacy analysis of anticancer drug delivery systems

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15324
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Doshisha Women's College of Liberal Arts
• Principal Investigator: Yamashita Shugo 同志社女子大学, 薬学部, 助教 (30845730)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 腫瘍組織内動態 / 体内動態制御 / 高分子ミセル / コンパートメントモデル / PK/PD

Outline of Final Research Achievements

In this study, we developed an analytical method to evaluate drug release and tumor retention from polymeric micelles in an environment closer to the biological environment with the aim of accurately determining the pharmacokinetics information about tumor distribution of small-molecule anticancer drugs, which is essential for achieving DDS-based cancer therapy. In addition, by utilizing a pharmacokinetic analysis method that combines tumor-bearing rats and tumor microdialysis, we were able to conduct a pharmacokinetic analysis focusing on anticancer drugs loaded on polymeric micelles and successfully established a PK/PD model that enables evaluation of the function versus effect of DDS technology.

Free Research Field

薬物動態

Academic Significance and Societal Importance of the Research Achievements

我々が考案した分析手法を活用することで、これまで解析が困難であった薬物キャリアに担持された低分子抗がん剤の腫瘍移行性に関する正確な速度論的情報の取得が期待できる。こうした薬物キャリアではなく担持された低分子に焦点を当てた速度論的情報は、DDS機能を客観的に評価するパラメータとして活用でき、DDS開発を加速させる方法論になり得る。以上のように、高精度なPK/PDモデルの構築を目指す本研究はDDS技術の機能対効果を多角的に評価可能にし、DDSの臨床応用へ向けた橋渡し研究への活用が期待できる。