濃度センシング機能を持つ世界初のドラッグデリバリーキャリア創製への挑戦

2015 Fiscal Year Research-status Report

• Project/Area Number: 15K15716
• Research Institution: Hokkaido University
• Principal Investigator: 阿部 薫明 北海道大学, 歯学研究科(研究院), 助教 (40374566)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ドラッグデリバリーシステム / 濃度センサー機能

Outline of Annual Research Achievements

低濃度時にのみ機能するドラッグデリバリーシステム（DDS）を開発することにより、
抗がん剤など副作用の強い薬剤も効果的に使用可能な、濃度センサー機能を有した
世界初のドラッグデリバリーシステムの開発を試みた。
DDSを実践するキャリアである多糖誘導体の分子構造が薬剤との会合状態に及ぼす影響を検討するため、リン酸化率や分子量を変えた数種類のリン酸化プルラン(PPL)やリン酸化マンナンを合成し、サイズ・形状・表面物性や会合状態の構造変化を検討した。徐放機構のモデル薬剤として抗菌物質CPC（塩化セチルピリジニウム）を用いたところ、
抗菌物質CPCのみでは高濃度でも洗浄後は十分な抗菌効果が得られなかったが、PPLとの複合体にすることにより、わずか100ppmの抗菌物質で優れた抗菌効果を発揮することが明らかになった。PPL-CPC複合体はCPC濃度200ppmでも優れた抗菌効果を発揮したが、高濃度で調整した複合体では抗菌効果を発現しなかった。これらの結果は、PPLを担体に用いた複合体が、低濃度時に機能し得る濃度センサー機能を有した画期的なドラッグデリバリーシステムの開発に向けて有用な物質であることが示唆された。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

目的としている低濃度時に機能する薬剤徐放機能を発現する薬剤-担体複合体のモデル物質の創製に成功した

Strategy for Future Research Activity

H２８年度は、濃度センサー機能の機構の解明、DDS機能の最適化を進めるとともに、細菌・細胞への効果の検討や、本担体の汎用性の検討も進めていく。

Causes of Carryover

平成２７年度中に購入し納品された物品の支払いが、２８年４月になったため

Expenditure Plan for Carryover Budget

上述の通り、既に使用決定済み

Research Products

• [Journal Article] Estimation of biocompatibility of nano-sized ceramic particles with osteoblasts, osteosarcomas and hepatocytes by static and time-lapse observation (2016)
  • Author(s): S. Abe, E. Seitoku, N. Iwadera, Y. Hamba, S. Yamagata, T. Akasaka, T. Kusaka, S. Inoue, Y. Yawaka, J. Iida, H. Sano, T. Yonezawa, and Y. Yoshida
  • Journal Title: J. Biomedical Nanotechnology Volume: 12 Pages: 472-480
  • DOI: 10.1166/jbn.2016.2190
  • Peer Reviewed
• [Journal Article] Evaluation of the biocompatibility of ceramic nanoparticles with A549 lung epithelial cells (2016)
  • Author(s): N. Kiyama, S. Abe, S. Yamagata, Y. Yoshida, and J. Iida
  • Journal Title: Nanoscience and Nanotechnology Letters Volume: 8 Pages: 310-315
  • DOI: 10.1166/nnl.2016.2132
  • Peer Reviewed
• [Journal Article] Assessment of size and morphological effects of ceramics nanoparticles on their biocompatibility (2016)
  • Author(s): S. Tsuchiya, S. Abe, Y. Era, Y. Nakagawa, M. Nakamura, T. Kusaka, Y. Yoshida, T. Yonezawa, and J. Iida
  • Journal Title: Nanoscience and Nanotechnology Letters Volume: 8 Pages: 329-334
  • DOI: 10.1166/nnl.2016.2139
  • Peer Reviewed
• [Journal Article] Development of poly(L-lactic acid)/organically modified montmorillonite nanocomposites for the fabrication of orthodontic anchoring screws (2016)
  • Author(s): K. Nakanishi, S. Yamagata, T. Akasaka, S. Abe, Y. Yoshida, and J. Iida
  • Journal Title: J. Nanoscience Nanotechnology Volume: 16 Pages: 9292-9297
  • DOI: 10.1166/jnn.2016.12917
  • Peer Reviewed
• [Journal Article] Density functional theory (DFT) study on ternary interaction system of fluorinated ethylene Carbonate, Li+, and graphene model (2016)
  • Author(s): M. Mutoh, S. Abe, T. Kusaka, M. Nakamura, Y. Yoshida, J. Iida, and H. Tachikawa
  • Journal Title: ATOMS Volume: 4 Pages: 401-408
  • DOI: 10.3390/atoms4010004
  • Peer Reviewed
• [Journal Article] Electronic States of Alkyl Radical-Functionalized C20 Fullerene: Density Functional Theory (DFT) Study (2016)
  • Author(s): S. Abe, S. Kawano, Y. Toida, M. Nakamura, S. Inoue, Y. Yoshida, H. Sano, H. Kawabata, and H. Tachikawa
  • Journal Title: Jpn. J. Applied Phys Volume: 55 Pages: 03DD0301-04
  • DOI: doi.org/10.7567/JJAP.55.03DD03
  • Peer Reviewed
• [Journal Article] Cytocompatibility of HeLa cells to nano-sized ceramics particles (2016)
  • Author(s): E. Seitoku, S. Abe, T. Kusaka, M. Nakamura, S. Inoue, Y. Yoshida and H. Sano
  • Journal Title: J. Nanoscience and Nanotechnology Volume: 16 Pages: 3373-3377
  • DOI: 10.1166/jnn.2016.12309
  • Peer Reviewed
• [Journal Article] Assessment of the inhibitory effects of fi ssure sealants on the demineralization of primary teeth using an automatic pH-cycling system (2016)
  • Author(s): S. Ushimura, K. Nakamura, Y. Matsuda, H. Minamikawa, S. Abe, and Y. Yawaka
  • Journal Title: Dental Material J. Volume: 35 Pages: 316-324
  • DOI: 10.4012/dmj2015-297
  • Peer Reviewed
• [Journal Article] Scanning Electron Microscope Observation of Carbon Nanotubes with Room Temperature Ionic Liquids: Effect of Their Hydrophilicities (2015)
  • Author(s): A. Hyono, S. Abe, K. Kawai, and T. Yonezawa
  • Journal Title: J. Nanoscience and Nanotechnology Volume: 15 Pages: 9272-9274
  • DOI: http://dx.doi.org/10.1166/jnn.2015.11409
  • Peer Reviewed
• [Journal Article] Firm attachment of carboxylated multi-walled carbon nanotubes onto amino-functionalized glass surface through ionic interaction (2015)
  • Author(s): Y. Konno, S. Abe, and T. Takada
  • Journal Title: Tanso Volume: 266 Pages: 7-10
  • DOI: http://dx.doi.org/10.7209/tanso.2015.7
  • Peer Reviewed
• [Journal Article] Effect of different remaining dentin thickness on Micro-tensile bond strength of current adhesive systems (2015)
  • Author(s): S. Ting, F. Pan, J. Fu , S. Kakuda, S. Hoshika, T. Ikeda, Y. Nakaoki, S. Abe, Y. Yohida and H. Sano
  • Journal Title: Dental Material J. Volume: 34 Pages: 181-188
  • DOI: 10.4012/dmj.2014-130
  • Peer Reviewed
• [Journal Article] Simple size-controlled preparation of micro-/nano-sized fullerene C60 particles using different chain-length diaminoalkane compounds (2015)
  • Author(s): M. Mutoh, S. Abe, K. Nakayama, S. Yoshizawa, M. Nakamura, T. Kusaka, Y. Yoshida J. Iida, and T. Takada
  • Journal Title: Nano Biomedicine Volume: 7 Pages: 87-92
  • DOI: 10.3390/atoms4010004
  • Peer Reviewed
• [Journal Article] Electroconductive pretreatment of several types of non-conductive wet biological samples for SEM using a room temperature ionic liquid: Simple and rapid conductive preparation (2015)
  • Author(s): M. Mutoh, S. Abe, A. Hyono, H. Matsuura, K. Nakanishi, K. Kawai, M. Nakamura, S. Inoue, Y. Yoshida J. Iida, and T. Yonezawa
  • Journal Title: Nano Biomedicine Volume: 7 Pages: 72-80
  • DOI: 10.3390/atoms4010004
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Electronic States of Alkyl Radical Functionalized Fullerene (R-C60): Density Functional Theory (DFT) Study (2016)
  • Author(s): S. Yoshizawa, S. Abe, T. Kusaka, M. Nakamura, Y. Yoshida, J. Iida and H. Tachikawa
  • Organizer: ISPlasma 2016
  • Place of Presentation: Nagoya, JAPAN
  • Year and Date: 2016-03-06 – 2016-03-10
  • Int'l Joint Research
• [Presentation] Preparation of size- and shape- controlled water-dispersible fullerene nanoparticles and their application in biological fields (2015)
  • Author(s): M. Mutoh, S. Abe, S. Yoshizawa, K. Nakayama, T. Kiba, Y. Yoshida, J. Iida, T Takada
  • Organizer: 第２５回日本MRS年次大会
  • Place of Presentation: 横浜, 横浜情報文化センター, 横浜市開港記念会館, 万国橋会議センター, 波止場会館, 産業貿易センタービル, 神奈川県民ホール, 横浜マリンタワー
  • Year and Date: 2015-12-08 – 2015-12-10
• [Presentation] Effective controlled drug release system using phosphorylated pullulans (2015)
  • Author(s): T. Okihara, S. Abe, Y. Okajima, S. Kamenoue, D. Yamamoto, S. Takashiba, Y. Yoshida
  • Organizer: NanoMED 2015
  • Place of Presentation: Manchester, UK
  • Year and Date: 2015-11-23 – 2015-11-25
• [Presentation] Static and time lapse observation for estimation of biocompatibility of nano-sized ceramic particles (2015)
  • Author(s): S Abe, N. Kiyama, S. Tsuchiya, T. Kiba, A. Murayama, Y. Yawaka, J. Iida, T. Yonezawa and Y. Yoshida
  • Organizer: NanoMED 2015
  • Place of Presentation: Manchester, UK
  • Year and Date: 2015-11-23 – 2015-11-25
• [Presentation] Cytocompatiblity of nano-sized ceramics particles on several cells (2015)
  • Author(s): S. Abe, N. Iwadera, M. Mutoh, T. Katsurayama, S. Morimoto, K. Nakanishi, J. Iida, and Y. Yoshida
  • Organizer: Boceramics 2015
  • Place of Presentation: Bali, INDNESIA
  • Year and Date: 2015-10-26 – 2015-10-28
  • Int'l Joint Research
• [Presentation] セラミックスナノ粒子の細胞安全性の評価 (2015)
  • Author(s): 阿部薫明
  • Organizer: 日本セラミックス協会 第１回ナノバイオセラミックスによる細胞機能制御テクノロジー研究会
  • Place of Presentation: 長岡, アオーレ長岡
  • Year and Date: 2015-08-21
  • Int'l Joint Research / Invited
• [Presentation] Interaction of Alkyl Radicals with Fullerene (C60): Density Functional Theory (DFT) Study (2015)
  • Author(s): S. Tsuchiya, N. Kiyama, S. Abe, T. Kiba, A. Murayama, J. Iida, and Y. Yoshida
  • Organizer: Nano Korea 2015
  • Place of Presentation: Seoul, KOREA
  • Year and Date: 2015-07-01 – 2015-07-03
  • Int'l Joint Research
• [Presentation] Preparation of surface-modified fullerene C60 microparticles (2015)
  • Author(s): S. Abe, M. Mutoh, K. Nakayama, K. Nakamura, T. Kusaka, Y. Yoshida, J. Iida, and T. Takada
  • Organizer: Nano Korea 2015
  • Place of Presentation: Seoul, KOREA
  • Year and Date: 2015-07-01 – 2015-07-03
  • Int'l Joint Research
• [Presentation] Interaction of Alkyl Radicals with Fullerene (C60): Density Functional Theory (DFT) Study (2015)
  • Author(s): S. Abe, S. Kawano, Y. Toida, S. Inoue, H. Sano, Y. Yoshida, and H. Tachikawa
  • Organizer: M & BE 2015
  • Place of Presentation: Tokyo, JAPAN
  • Year and Date: 2015-06-22 – 2015-06-25
  • Int'l Joint Research
• [Remarks]
  • URL: http://www.den.hokudai.ac.jp/contents/compendium/zairyou/