Development of intelligent formulations for controlling drug release: a UGT1A1-based strategy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15526
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Yokohama College of Pharmacy
• Principal Investigator: Isobe Takashi 横浜薬科大学, 薬学部, 講師 (30440530)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: アルギン酸 / UGT1A1 / ビリルビン

Outline of Final Research Achievements

It is difficult to predict the activity of metabolic enzymes in patients taking multiple concomitant drugs (e.g., elderly patients) owing to the drugs’ possible effects on induction and inhibition of metabolic those enzymes. Therefore, intelligent formulations are being developed that adjust drug release based on metabolic enzyme activity. In the present study, we aimed to develop an oral formulation that controls drug release by assessing uridine diphosphate glucuronosyltransferase 1A1 activity in the liver based on intestinal bilirubin concentration. We prepared alginate gel beads that released drugs at varying rates depending on the bilirubin concentration. Results showed that the drug release profile of alginate gel beads in the presence of bilirubin was affected by the molecular weight of alginic acid, calcium concentration at the time of preparation, and gelation time.

Free Research Field

薬物代謝学、製剤学

Academic Significance and Societal Importance of the Research Achievements

世界に先駆けて超高齢化社会に突入した日本において、高齢者への安全な薬物療法は国民のQOL（生活の質）の向上を考える上で重要です。服用薬が多く、薬による代謝酵素の変動を予測しづらい高齢者は副作用発生のリスクも高くなる傾向にあります。本研究で得られた成果は、患者ごとの代謝酵素の変動を把握し適切な量の薬物を放出するインテリジェント製剤の開発において有益な情報であり、この成果が高齢者など副作用発生リスクの高い患者への安全安心な薬の提供に役立つと考えております。