Development of intelligent drug-delivery systems controlled under external stimulation with NIR irradiation

• Project/Area Number: 18K09616
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Nagasaki University (2019-2022); Hokkaido University (2018)
• Principal Investigator: ABE Shigeaki 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (40374566)
• Co-Investigator(Kenkyū-buntansha): 高田 知哉 公立千歳科学技術大学, 理工学部, 准教授 (00342444) ; 兵野 篤 旭川工業高等専門学校, 物質化学工学科, 助教 (20554299) ; 木場 隆之 北見工業大学, 工学部, 准教授 (40567236) ; 玉井 美保 北海道大学, 歯学研究院, 助教 (20619704) ; 江良 裕子 埼玉県立大学, 保健医療福祉学部, 助教 (00825309) ; 成徳 英理 北海道大学, 歯学研究院, 学術研究員 (00829393)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 薬剤徐放 / ゾル-ゲル / 赤外照射 / 外部刺激 / ハイドロゲル / 非侵襲性 / 赤外応答性 / ゾルーゲル / 外部刺激応答 / 光熱変換 / インテリジェントDDS

Outline of Final Research Achievements

We have investigated a hydrogel composite that undergoes a sol-gel phase transition under external stimulation. Obtained polyacrylamide-based hydrogel composite showed a reversible sol-gel phase transition during the heating-cooling process. In order to use infrared light as an external stimulus for controlling the phase transition process, we prepared hydrophilic carbon nanotubes (CNT) derivatives with surface chemical modification because CNTs are known to have effective photothermal conversion properties. Then we prepared a composite material with hydrogel. made. The obtained material indicated efficiently sol transition by infrared light irradiation and exhibited a reversible sol-gel phase transition. Release of the model drug was also confirmed by the transition. Based on these results, we succeeded in prototyping a novel material that exhibits a sol-gel phase transition upon irradiation with infrared light and enables drug release.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として得られた赤外光照射により薬剤徐放を可能とする新規ハイドロゲル複合材料は、薬剤の投与を必要とするタイミングに、開腹などの外科的な侵襲を与えず、且つ大型の装置の使用を必要とせずに、小型の赤外光源を用いることで簡便に薬剤の放出を可能とする材料である。用いた材料は既に医療材料として使用されている化合物や、安全性の検討がなされている物質であり、医療応用への展開も期待できる。この技術により、歯科のみならず医学領域においても、非侵襲的に効果的な薬剤の投与を可能とするため、患者のQOLの向上への貢献が期待される。

Research Products

• [Journal Article] A novel thermos responsible hydrogel composite: Controlled by infra-red irradiation (2023)
  • Author(s): S. Abe, M. NNesabi, S. Safaee, E. Seitoku, Y. Yato, A. Hyono, K. Nakanishi, Y. Era, M. Nakamura, T. Kusaka, A. Valanezhad, T. Takada, and I. Watanabe
  • Journal Title: Molecular Crystals and Liquid Crystals Volume: 755 Issue: 1 Pages: 1-7
  • DOI: 10.1080/15421406.2023.2194600
  • Peer Reviewed
• [Journal Article] Comparative evaluation of three nanofilled resin-based dental composites: cytotoxicity, surface roughness and flexural properties (2022)
  • Author(s): S. Jafarnia, A. Valanezhad*, T. Odatsu, M. Nesabi, S. Safaee, S. Abe, M. Khodaei, S. Shahabi, and I. Watanabe
  • Journal Title: Polymers and Polymer Composites Volume: 30 Pages: 1-8
  • DOI: 10.1177/09673911221087586
  • Peer Reviewed / Open Access
• [Journal Article] A novel coating layer on zirconia using modified zinc phosphatizing method (2021)
  • Author(s): KODAMA Kouta、VALANEZHAD Alireza、KHODAEI Mohammad、SAFAEE Sirus、JAFARNIA Shiva、NESABI Mahdis、ABE Shigeaki、WATANABE Ikuya、MURATA Hiroshi
  • Journal Title: Dental Materials Journal Volume: 40 Issue: 4 Pages: 870-876
  • DOI: 10.4012/dmj.2020-253
  • NAID: 130008069736
  • ISSN: 0287-4547, 1881-1361
  • Year and Date: 2021-07-25
  • Peer Reviewed / Open Access
• [Journal Article] Fabrication of bioactive glass coating on pure titanium by sol-dip method: Dental applications (2021)
  • Author(s): SAFAEE Sirus、VALANEZHAD Alireza、NESABI Mahdis、JAFARNIA Shiva、SANO Hideaki、SHAHABI Sima、ABE Shigeaki、WATANABE Ikuya
  • Journal Title: Dental Materials Journal Volume: 40 Issue: 4 Pages: 949-956
  • DOI: 10.4012/dmj.2020-323
  • NAID: 130008069758
  • ISSN: 0287-4547, 1881-1361
  • Year and Date: 2021-07-25
  • Peer Reviewed / Open Access
• [Journal Article] Physical and mechanical characteristics of short fiber-reinforced resin composite in comparison with bulk-fill composites (2021)
  • Author(s): Jafarnia Shiva、Valanezhad Alireza、Shahabi Sima、Abe Shigeaki、Watanabe Ikuya
  • Journal Title: Journal of Oral Science Volume: 63 Issue: 2 Pages: 148-151
  • DOI: 10.2334/josnusd.20-0436
  • NAID: 130008009607
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] A novel multi-structural reinforced treatment on Ti implant utilizing a combination of alkali solution and bioactive glass sol (2021)
  • Author(s): Nesabi Mahdis、Valanezhad Alireza、Safaee Sirus、Odatsu Tetsurou、Abe Shigeaki、Watanabe Ikuya
  • Journal Title: Journal of the Mechanical Behavior of Biomedical Materials Volume: 124 Pages: 104837-104837
  • DOI: 10.1016/j.jmbbm.2021.104837
  • Peer Reviewed / Open Access
• [Journal Article] Ion Capture and Release Ability of Glass Ionomer Cement Containing Nanoporous Silica Particles with Different Pore and Particle Size (2021)
  • Author(s): Endo Ryoshun、Nakanishi Ko、Bando Yosuke、Abe Shigeaki、Maruoka Haruhi、Nakamura Mariko、Akasaka Tsukasa、Yoshida Yasuhiro、Sato Yoshiaki
  • Journal Title: Materials Volume: 14 Issue: 19 Pages: 5742-5742
  • DOI: 10.3390/ma14195742
  • Peer Reviewed / Open Access
• [Journal Article] Bone Formation Ability and Cell Viability Enhancement of MC3T3-E1 Cells by Ferrostatin-1 a Ferroptosis Inhibitor of Cancer Cells (2021)
  • Author(s): Valanezhad Alireza、Odatsu Tetsurou、Abe Shigeaki、Watanabe Ikuya
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 22 Pages: 12259-12259
  • DOI: 10.3390/ijms222212259
  • NAID: 120007186858
  • Peer Reviewed / Open Access
• [Journal Article] Fabrication of infrared-responsive carbon nanotube coating on glass surface through covalent bond formation using photoreactive silane coupling agent (2020)
  • Author(s): T. Takada, Y. Kitamura, S. Takakuwa
  • Journal Title: Journal of the Ceramic Society of Japan Volume: 128 Issue: 12 Pages: 1066-1071
  • DOI: 10.2109/jcersj2.20152
  • NAID: 130007949045
  • ISSN: 1348-6535, 1882-0743
  • Year and Date: 2020-12-01
  • Peer Reviewed
• [Journal Article] Thermoresponse of poly(acrylamide-<i>co</i>-butyl methacrylate)/polyacrylic acid/MWCNT composite hydrogels observed by infrared irradiation (2020)
  • Author(s): T. Takada
  • Journal Title: TANSO Volume: 2020 Issue: 295 Pages: 135-139
  • DOI: 10.7209/tanso.2020.135
  • NAID: 130007955928
  • ISSN: 0371-5345, 1884-5495
  • Year and Date: 2020-11-15
  • Peer Reviewed
• [Journal Article] Self-assembled monolayer formation on a dental orthodontic stainless steel wire surface to suppress metal ion elution (2020)
  • Author(s): H. Tamaki, S. Abe, S. Yamagata, Y. Yoshida, and Y. Sato
  • Journal Title: Coatings Volume: 20 Issue: 4 Pages: 36701-09
  • DOI: 10.3390/coatings10040367
  • NAID: 120006988210
  • Peer Reviewed / Open Access
• [Journal Article] Bonding performance of a hydrophilic amide monomer containing adhesive to occlusal and cervical dentin (2020)
  • Author(s): E. Seitoku, S. Hoshika, T. Ikeda, S. Abe, T. Tanaka, and H. Sano
  • Journal Title: Materials Volume: 13 Issue: 21 Pages: 472701-08
  • DOI: 10.3390/ma13214727
  • Peer Reviewed
• [Journal Article] Fractal dimensional analysis on dispersion/aggregation state of MWCNT in poly(4-chloromethyl)styrene: effect of UV-induced polymer-MWCNT chemical bond formation and its influence in electrical conductivity of their composites (2020)
  • Author(s): Tomoya Takada, Ryoga Ushiromura, Takuto Fushiki
  • Journal Title: International Journal of Polymer Analysis and Characterization Volume: 25 Issue: 4 Pages: 252-261
  • DOI: 10.1080/1023666x.2020.1783079
  • Peer Reviewed
• [Journal Article] Size- and morphology- controlled preparation of surface-modified waterdispersible fullerene nanoparticles for bioapplications (2020)
  • Author(s): H. Oguma, E. Seitoku, M. Mutoh, S. Yoshizawa, K. Nakanishi, Y. Bando, Y. Era, T. Kiba, P. Saikaew, M. Tamai, T. Akasaka, M. Nakamura, T. Kusaka, Y. Yoshida, Y. Sato, H. Sano, S. Abe, .A. Valanezhad, I. Watanabe, S. Inoue, and T. Takada
  • Journal Title: J. Nanoscience and Nanotechnology Volume: 20 Issue: 5 Pages: 2668-2674
  • DOI: 10.1166/jnn.2020.17473
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fabrication and characterization of microcavity organic light-emitting diode with CaF2/ZnS distributed Bragg reflector (2020)
  • Author(s): T. Kitabayashi, T. Asashita, N. Satoh, T. Kiba, M. Kawamura, Y. Abe, K.H. Kim
  • Journal Title: Thin Solid Films Volume: 699 Pages: 13791201-06
  • DOI: 10.1016/j.tsf.2020.137912
  • Peer Reviewed / Open Access
• [Journal Article] Size dependence of emission enhancement of Tris(8-hydroxyquinolinato) aluminum with plasmonic Al nanostructure (2020)
  • Author(s): N. Iijima, M. Ugajin, T. Kiba, M. Kawamura, Y. Abe, K.H. Kim, A. Higo, J. Takayama S. Hiura, A. Murayama
  • Journal Title: Thin Solid Films Volume: 700 Pages: 13792001-08
  • DOI: 10.1016/j.tsf.2020.137920
  • Peer Reviewed / Open Access
• [Journal Article] Surface-engineered design of efficient luminescent europium(III) complex-based hydroxyapatite nanocrystals for rapid HeLa cancer cell imaging (2019)
  • Author(s): T. Kataoka, S. Abe, and M. Tagaya
  • Journal Title: ACS Applied Materials & Interfaces Volume: 11 Issue: 9 Pages: 8915-8927
  • DOI: 10.1021/acsami.8b22740
  • Peer Reviewed
• [Journal Article] Electric Charge Dependence of Controlled Dye-Release Behavior in Glass Ionomer Cement Containing Nano-Porous Silica Particles (2018)
  • Author(s): Bando Y, Nakanishi K, Abe S, Yamagata S, Yoshida Y, Iida J
  • Journal Title: Journal of Nanoscience and Nanotechnology Volume: 18 Issue: 1 Pages: 75-79
  • DOI: 10.1166/jnn.2018.14618
  • Peer Reviewed
• [Journal Article] Calcium charge and release of conventional glass-ionomer cement containing nano porous silica (2018)
  • Author(s): K. Nakamura, S. Abe, H. Minamikawa, and Y. Yawaka
  • Journal Title: Materials Volume: 11, Issue: 8 Pages: 129501-129508
  • DOI: 10.3390/ma11081295
  • Peer Reviewed
• [Journal Article] Chemical modification to suppress metal ions elution of dental orthodontic wire surface (2018)
  • Author(s): H. Tamaki, S. Tsuchiya, Y. Sakurada, S. Yamagata, A. Hyono, K. Kaneko, K. Kawai, S. Abe, Y. Yoshida, and J. Iida
  • Journal Title: Molecular Crystals and Liquid Crystals Volume: 660 Issue: 1 Pages: 163-172
  • DOI: 10.1080/15421406.2018.1457279
  • Peer Reviewed
• [Journal Article] Optical and Chromatic Evaluation of Fluorescent Orthodontic Bonding Materials Doped with a Europium β-diketonate Complex (2018)
  • Author(s): A. Matsumoto, S. Yamagata, S. Abe, T. Akasaka, Y. Yoshida, and J. Iida
  • Journal Title: Nano Biomedicine Volume: 10 Issue: 1 Pages: 3-8
  • DOI: 10.11344/nano.10.3
  • NAID: 130007438742
  • ISSN: 1883-5198, 2185-4734
  • Peer Reviewed
• [Journal Article] Optical and chromatic evaluation of fluorescent orthodontic bonding materials doped with a europium β-diketonate complex (2018)
  • Author(s): M. Nishimoto, S. Abe, and T. Yonezawa
  • Journal Title: New J. Chemistry Volume: 42 Issue: 17 Pages: 14493-14501
  • DOI: 10.1039/c8nj01747f
  • NAID: 130007438742
  • Peer Reviewed
• [Journal Article] Preparation of calcium phosphate nanoparticles hybridized with europium(III) complex for novel luminescent organic-inorganic systems (2018)
  • Author(s): M. Tagaya, S. Abe, K,i Shinozaki, and T. Kataoka
  • Journal Title: J. Physics and Chemistry of Solids Volume: 122 Pages: 218-226
  • DOI: 10.1016/j.jpcs.2018.06.031
  • Peer Reviewed
• [Journal Article] Fabrication of Light-curing Type Fluorescent Orthodontic Bonding Materials using Europium-β-diketonate Complex (2018)
  • Author(s): S. Yamagata, T. Yamamoto, Y. Sato, S. Abe, T. Akasaka, and Y. Yoshida
  • Journal Title: Nano Biomedicine Volume: 10 Issue: 2 Pages: 53-60
  • DOI: 10.11344/nano.10.53
  • NAID: 130007607966
  • ISSN: 1883-5198, 2185-4734
  • Peer Reviewed
• [Presentation] A novel drug releaseable dental materials using nano-structured silica particles (2022)
  • Author(s): S. Abe, M. Nesabi, S. Safaee, S. Iwata, Y. Era, Y. Yatoh, A. Hyono, A. Valanezhad, and I. Watanabe
  • Organizer: International Dental Material Congress 2022
  • Int'l Joint Research
• [Presentation] 脱炭酸酵素(Carbonic Anhydrase)活性中心を模倣した酵素モデル化合物を用いた石灰化反応の制御 (2022)
  • Author(s): 阿部薫明、江良裕子、高田知哉
  • Organizer: 第4９回有機典型化学討論会
• [Presentation] Molecular Design of Organic Radical-Functionalized Graphene: Density Functional Theory (DFT) Study (2022)
  • Author(s): S. Abe, I. Watanabe, and H. Tachikawa
  • Organizer: MNC2022
  • Int'l Joint Research
• [Presentation] Development of thermos responsible composite hydrogels using Carbon Nanotube derivatives (2021)
  • Author(s): Shigeaki Abe, Yuko Era, Alireza Valanezhad, Mariko Nakamura, Tomoya Takada, and Ikuya Watanabe
  • Organizer: KJF-ICOMEP 2021
  • Int'l Joint Research
• [Presentation] Sustainable drug-release property of dental resin composite using nano-porous silica particles (2021)
  • Author(s): Sirus Safaee, Mahdis Nesabi, Shiva Jafarnia, Alireza Valanezhad, Yuko Era, Shigeaki Abe, and Ikuya Watanabe
  • Organizer: 第78回日本歯科理工学会
• [Presentation] 薬剤徐放能を持つ歯科用コンポジット材料の開発 (2021)
  • Author(s): 阿部薫明 ,遠藤諒俊, Mahdis Nesabi,Sirus Safaee,Shiva Jafarnia, 岩沼健児, 成徳英理, 中西 康, 江良祐子, Alireza Valanezhad, 中村光一, 高田知哉, 佐藤嘉晃, 渡邊郁哉
  • Organizer: 第43回日本バイオマテリアル学会大会
• [Presentation] ポリアクリルアミド/ポリアクリル酸/ＭＷＣＮＴ複合ハイドロゲルの作製と赤外線応答性 (2021)
  • Author(s): 高田知哉、早坂勇輝、阿部薫明
  • Organizer: 日本化学会第101回春年会
• [Presentation] Eu(III)錯体を含有したハイドロキシアパタイトナノ粒子の合成と葉酸修飾による細胞標識機能化 (2021)
  • Author(s): 片岡卓也、阿部薫明、多賀谷基博
  • Organizer: 日本セラミックス協会2021年年会
• [Presentation] 温度応答により薬剤徐放性を示すハイドロゲルコンポジット材料の開発 (2020)
  • Author(s): 阿部薫明, 江良裕子, 中西 康, Valanezhad Alireza, 渡邊郁哉
  • Organizer: 第75回日本歯科理工学会
• [Presentation] ナノ多孔質物質を用いた薬剤徐放能を持つ新規な歯科修復材料の開発 (2020)
  • Author(s): 成徳英理、江良裕子、阿部薫明、佐野英彦
  • Organizer: 化学系学協会北海道支部2020年冬季研究発表
• [Presentation] カゴ状ナノシリカ粒子を用いた薬剤徐放性歯科材料の開 (2019)
  • Author(s): 江良裕子，阿部薫明，赤坂司，吉田靖弘
  • Organizer: 第73回;日本歯科理工学会学術講演
• [Presentation] Multifunctional surface modification on dental orthodontic wire surface: Suppression of metal ions elution and antibacterial property (2019)
  • Author(s): H. Tamaki, S. Abe, S. Yamagata, Y. Yoshida, J. Iida and Y. Sato
  • Organizer: Nano Korea 2019
  • Int'l Joint Research
• [Presentation] ナノポーラス物質含有による歯科用シーラント材料から薬剤徐放特性の検討 (2019)
  • Author(s): 江良裕子，中西 康，阿部薫明，玉井美保，赤坂 司，吉田靖弘
  • Organizer: 第74回日本歯科理工学会学術講演
• [Presentation] Drug release behavior from dental/medical materials using nanoporous silica (2019)
  • Author(s): Y. Era, F. Farhana, S. Iwata, S. Abe, M. Nakamura, I. Watanabe, and Y. Yoshida
  • Organizer: Chitose International Forum 2019
  • Int'l Joint Research
• [Presentation] ナノ多孔質シリカの孔サイズがもたらすイオン放出能への影響 (2019)
  • Author(s): 遠藤諒俊、中西 康、坂東洋祐、松本愛子、阿部薫明、山方秀一、吉田靖弘、佐藤嘉晃
  • Organizer: 第78回日本矯正歯科学会学術大会
• [Presentation] Model drug-released behavior from medical materials using nanoporous silica (2019)
  • Author(s): E. Seitoku, K. Nakanishi, Y. Bandoh, Y. Era, S. Iwata, S. Abe, M. Nakamura, I. Watanabe, and H. Sano
  • Organizer: 19th Asian BioCeramics Symposium
  • Int'l Joint Research
• [Presentation] カゴ状ナノシリカ粒子を用いた薬剤徐放性歯科材料の開発 (2019)
  • Author(s): 江良裕子，阿部薫明，赤坂司，吉田靖弘
  • Organizer: 第73回歯科理工学春季学術討論会
• [Presentation] Photoluminescent and biocompatible property of folic acid derivative immobilized apatite/Eu-complex hybrid particles for biomedical tool (2018)
  • Author(s): S. Abe, T. Kataoka M. Tagaya
  • Organizer: NanoKorea 2018
  • Int'l Joint Research
• [Presentation] Cytocompatibility of nano-porous silica using for novel controlled drug-release materials (2018)
  • Author(s): E. Seitoku, S. Abe, Y. Banjo, K. Nakanishi, S. Kakuda, J. Iida, Y. Yoshida, H. Sano
  • Organizer: IADR-PER 2018
• [Presentation] Size- and morphology- controlled preparation of surface-modified water-dispersible fullerene nanoparticles for bioapplications (2018)
  • Author(s): Y. ERA, E. SEITOKU, S. ABE, T. KIBA, M. NAKAMURA, Teruo KUSAKA,, S. INOUE, Y. YOSHIDA, H. SANO, and T. TAKADA
  • Organizer: KJF
• [Presentation] 多孔質シリカを用いた選択的薬剤徐放を実現する歯科用材料の開発 (2018)
  • Author(s): 江良裕子，中西康，阿部薫明，玉井美保，赤坂司，吉田靖弘
  • Organizer: 第72回歯科理工学秋季学術討論会
• [Presentation] Controlled drug release property of nano-porous silica micro particles and their cytocompatibility (2018)
  • Author(s): E. Seitoku, Y. Era, S. Abe, M. Nakamura, T. Kusaka, S. Inoue, Y. Yoshida, H. Sano
  • Organizer: Bioceramics 30
  • Int'l Joint Research