Development of dual pH-responsive drug delivery career by the logical design of polymer

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18846
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Keio University
• Principal Investigator: Hiruta Yuki 慶應義塾大学, 薬学部(芝共立), 助教 (60710944)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 温度 / pH / 機能性高分子 / ミセル / DDS / 抗がん剤 / ナノ材料

Outline of Final Research Achievements

We report a polymeric micelle drug delivery system, which enables selective intracellular uptake with external thermal stimulation, and effective release of a drug at internal acidic endosomal pH. We developed dual temperature- and pH-responsive polymeric micelle encapsulated anti-cancer agent, doxorubicin (DOX). The resultant micelle exhibited a temperature-dependent phase transition at a temperature slightly higher than body temperature, and intracellular uptake of encapsulated DOX was accelerated above phase transition temperature. The cytotoxicity of doxorubicin (DOX)-loaded dual temperature- and pH-responsive micelles against human cervical cancer HeLa cells was significantly greater at 42 °C than at 37 °C, This proof-of-concept synergistic two-step delivery system with enhanced intracellular uptake upon external thermal stimulation and rapid release of DOX at internal acidic endosomal pH was effective against tumor cells in vitro.

Free Research Field

物理系薬学