An insulin molecular machine whose pharmacokinetics is controllable in subcutaneous tissue and its possibility for hybrid artificial pancreas

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Josai University
• Principal Investigator: Egawa Yuya 城西大学, 薬学部, 准教授 (90400267)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: フェニルボロン酸 / インスリン / 血糖値 / 交互累積膜 / 糖鎖 / DDS / 分子マシン

Outline of Final Research Achievements

We have prepared phenylboronic acid-modified insulin (PBA-Ins) which has glucose-lowering effect and attempted to control its pharmacokinetics by utilizing the binding between PBA and sugar chains. As a model of sugar chains, poly(vinyl alcohol) (pVA) was used because it also binds with PBA. pVA was coated on the surface of an electrode of quartz crystal microbalance (QCM), and it was immersed in a solution of PBA-Ins. The QCM result confirmed adsorption of PBA-Ins on the pVA surface. In addition, a layer-by-layer (LbL) film composed of pVA and PBA-Ins was successfully prepared because there are two PBA moieties in one PBA-Ins molecules. By using the LbL film, we confirmed that the adsorbed PBA-Ins was released in the presence of fructose. These results show that PBA modified drugs have a potential to become a molecular machine whose destination can be controlled depending on the presence or absence of sugars. This study provides the working principle of the molecular machine.

Free Research Field

物理化学

Academic Significance and Societal Importance of the Research Achievements

本研究では細胞表面モデルとして用いたpVA上でPBA-Insを吸着，脱着させることに成功した。このPBA-Insを皮下組織に投与した場合，PBA-Insは皮下組織の脂肪細胞などの糖鎖と結合すると予想される。ここに糖類を追加することにより，PBA-Insを脱着させ，血中に送り込むことができると考えられる。すなわち，PBA修飾薬物は糖類の有無により，行き先をコントロールできる分子マシン製剤になる可能性を持ち，その動作原理を本研究で構築できたといえる。