Challenge to the world's first drug delivery system having a drug-concentration sensing function

• Project/Area Number: 24659873
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Okayama University
• Principal Investigator: YOSHIDA Yasuhiro 岡山大学, 歯学部, 博士研究員 (90281162)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ドラッグデリバリーシステム / DDS / 担体 / リン酸化プルラン / 塩化セチルピリジニウム / CPC / 濃度 / 抗菌 / 多糖誘導体 / リン酸化多糖 / ミセル / 抗菌剤 / 高度変化 / 濃度変化 / イオン結合 / 疎水性相互作用

Research Abstract

To develop the world's first drug delivery system having a drug-concentration sensing function, we synthesized phosphorylated pullulan (PPL) with several phosphorylation ratios as the carrier for bactericide delivery. Only cetylpyridinium chloride (CPC) showed no effect on bacterial growth after slight rinsing, even at a high concentration of CPC. However, it was revealed that the complex of 0.01% PPL and 0.01% CPC (0.01% PPL-CPC) consistently exhibited an antibacterial effect, even after rinsing with distilled water. Although 0.02% PPL-CPC also showed an excellent antibacterial effect like 0.01% PPL-CPC, 0.03, 0.04 and 0.05% PPL-CPC have no effect on bacterial growth after slight rinsing. These facts indicated that PPL is available as a carrier for drug delivery system having a drug-concentration sensing function.

Research Products

• [Journal Article] Novel fluoro-carbon functional monomer for dental bonding (2014)
  • Author(s): Yoshihara K, Yoshida Y, Hayakawa S, Nagaoka N, Kamenoue S, Okihara T, Ogawa T, Nakamura M, Osaka A, Van Meerbeek B
  • Journal Title: J Dent Res Volume: 93(2) Issue: 2 Pages: 189-94
  • DOI: 10.1177/0022034513514447
  • Peer Reviewed
• [Journal Article] A novel, visible light-induced, rapidly cross-linkable gelatin scaffold for osteochondral tissue engineering (2014)
  • Author(s): Tetsuro Mazaki, Yasuyuki Shiozaki, Kentaro Yamane, Aki Yoshida, Mariko Nakamura, Yasuhiro Yoshida, Di Zhou, Takashi Kitajima, Masato Tanaka, Yoshihiro ito, Toshifumi Ozaki, and Akihiro Matsukawa
  • Journal Title: Sci. Rep. Volume: 4 Issue: 1 Pages: 4457-4457
  • DOI: 10.1038/srep04457
  • NAID: 120005526619
  • Peer Reviewed
• [Journal Article] Mussel-inspired human gelatin nanocoating for creating biologically adhesive surfaces (2014)
  • Author(s): Yang, X., Zhu, L., Tada, S., Zhou, D., Kitajima, T., Isoshima, T., Yoshida, Y., Nakamura, M., Yan, W., Ito, Y
  • Journal Title: International Journal Nanomedicine Volume: 29 Pages: 2753-2765
  • DOI: 10.2147/ijn.s60624
  • Peer Reviewed
• [Journal Article] In vitro and in vivo enhanced osteogenesis by kaempferol found by a high-throughput assay using human mesenchymal stromal cells (2014)
  • Author(s): Tetsuro Mazaki, Takashi Kitajima, Yasuyuki Shiozaki, Miwa Sato, Megumi Mino, Aki Yoshida, Mariko Nakamura, Yasuhiro Yoshida, Masato Tanaka, Toshifumi Ozaki, Akihiro Matsukawa and Yoshihiro Ito
  • Journal Title: J. Func. Foods Volume: 6 Pages: 241-247
  • DOI: 10.1016/j.jff.2013.10.013
  • Peer Reviewed
• [Journal Article] Hybrid sponge comprised of galactosylated chitosan and hyaluronic acid mediates the co-culture of hepatocytes and endothelial cells (2014)
  • Author(s): Shang, Y., M. Tamai, R. Ishii, N. Nagaoka, Y. Yoshida, M. Ogasawara, J. Yang, Y. Tagawa
  • Journal Title: J. Biosci. Bioeng. Volume: 117 Issue: 1 Pages: 99-106
  • DOI: 10.1016/j.jbiosc.2013.06.015
  • Peer Reviewed
• [Journal Article] Bone-tissue response to implant surfaces functionalized with phosphate-containing polymers (2014)
  • Author(s): Cardoso, M. V., Chaudhari, A., Yoshida, Y., Van Meerbeek, B., Naert, I., Duyck, J
  • Journal Title: Clinical Oral Implants Research Volume: 25 Pages: 91-100
  • Peer Reviewed
• [Journal Article] Phosphorylated gelatin to enhance cell adhesion to titanium (2013)
  • Author(s): Park, S. H., Zhu, L., Tada, S., Obuse, S., Yoshida, Y., Nakamura, M., Son, T. II, Tsuneda, S., Ito, Y
  • Journal Title: Polymer International Volume: (in press) Issue: 9 Pages: 1616-1619
  • DOI: 10.1002/pi.4647
  • Year and Date: 2013-12-12
  • Peer Reviewed
• [Journal Article] Adhesive interfacial interaction affected by different carbon-chain monomers (2013)
  • Author(s): Yoshihara K, Yoshida Y, Nagaoka N, Hayakawa S, Okihara T, De Munck J, Maruo Y, Nishigawa G, Minagi S, Osaka A, Van Meerbeek B
  • Journal Title: Dent Mater Volume: 29(8) Issue: 8 Pages: 888-97
  • DOI: 10.1016/j.dental.2013.05.006
  • Peer Reviewed
• [Journal Article] Enhanced in vivo osteogenesis by nanocarrier-fused BMP4 (2013)
  • Author(s): Y. Shiozaki
  • Journal Title: Int. J. Nanomed. Volume: 8 Pages: 1349-1360
  • DOI: 10.2147/ijn.s44124
  • Peer Reviewed
• [Journal Article] Flavonol-containing phosphorylated pullulan may attenuate pulp inflammation (2013)
  • Author(s): J. Yonehiro
  • Journal Title: Int. Endod. J. Volume: 46 Issue: 2 Pages: 119-127
  • DOI: 10.1111/j.1365-2591.2012.02095.x
  • Peer Reviewed
• [Journal Article] 歯質に対する接着耐久性を考える-アパタイトとの化学的相互作用-.DE(Dental Engineering) (2013)
  • Author(s): 吉田靖弘, 吉原久美子, 井上哲
  • Journal Title: 日本歯科理工学会誌 Volume: 32 Pages: 257-260
• [Journal Article] BMP-2 gene transfer under various conditions with in vivo electroporation and bone induction (2012)
  • Author(s): Hiromitsu Yamamoto, Mariko Kawai, 他8名
  • Journal Title: Asian Journal of Oral and Maxillofacial Surgery Volume: 24 Issue: 1 Pages: 49-53
  • DOI: 10.1016/j.ajoms.2011.10.006
  • Peer Reviewed
• [Journal Article] Establishment of ex vivo pulpitis model by co-culturing immortalized dental pulp cells and macrophages (2012)
  • Author(s): J. Yonehiro
  • Journal Title: Int. Endod. J. Volume: 45 Issue: 12 Pages: 1103-1108
  • DOI: 10.1111/j.1365-2591.2012.02074.x
  • Peer Reviewed
• [Journal Article] HEMA inhibits interfacial nano-layering of the functional monomer MDP (2012)
  • Author(s): Yoshida Y, Yoshihara K, Hayakawa S, Nagaoka N, Okihara T, Matsumoto T, Minagi S, Osaka A, Van Landuyt K, Van Meerbeek B
  • Journal Title: J Dent Res Volume: 91(11) Issue: 11 Pages: 1060-5
  • DOI: 10.1177/0022034512460396
  • Peer Reviewed
• [Journal Article] X-ray diffraction analysis of three-dimensional self-reinforcing monomer and its chemical interaction with tooth and hydroxyapatite (2012)
  • Author(s): Yoshida, Y., Yoshihara, K., Nagaoka, N., Hanabusa, M., Momoi, Y
  • Journal Title: Dental Materials Journal Volume: 31 Issue: 4 Pages: 697-702
  • DOI: 10.4012/dmj.2012-074
  • NAID: 10030502018
  • ISSN: 0287-4547, 1881-1361
  • Peer Reviewed
• [Journal Article] Osteoblast compatibility of materials depends on serum protein absorbability in osteogenesis (2012)
  • Author(s): Kenichi Harimoto, Yasuhiro Yoshida, Kumiko Yoshihara, Noriyuki Nagaoka, Takuya Matsumoto, Yoh-ichi Tagawa
  • Journal Title: Dental Materials Journal Volume: 31 Issue: 4 Pages: 674-680
  • DOI: 10.4012/dmj.2012-075
  • NAID: 10030501890
  • ISSN: 0287-4547, 1881-1361
  • Peer Reviewed
• [Journal Article] Preparation of low-crystalline apatite nanoparticles and their coating onto quartz substrates (2012)
  • Author(s): M. Kawashita
  • Journal Title: J. Mater. Sci. Mater. Med. Volume: 23 Issue: 6 Pages: 1355-1362
  • DOI: 10.1007/s10856-012-4614-6
  • Peer Reviewed
• [Journal Article] Effect of low-shrinking composite on the bonding effectiveness of two adhesives in occlusal Class-I cavities (2012)
  • Author(s): Mine, A., De Munck, J., Cardoso, M. V., Van Landuyt, K. L., Poitevin, A., Kuboki, T., Yoshida, Y., Suzuki, K., Van Meerbeek, B
  • Journal Title: Dental Materials Journal Volume: 31 Issue: 3 Pages: 418-426
  • DOI: 10.4012/dmj.2011-261
  • NAID: 10030315288
  • ISSN: 0287-4547, 1881-1361
  • Peer Reviewed
• [Journal Article] Self-assembled Nano-layering at the Adhesive Interface (2012)
  • Author(s): Y.Yoshida
  • Journal Title: Journal of Dental Research Volume: 91 Issue: 4 Pages: 376-381
  • DOI: 10.1177/0022034512437375
  • Peer Reviewed
• [Journal Article] 接着と合着を再考する―歯質接着のためのナノ界面分析― (2012)
  • Author(s): 吉田靖弘
  • Journal Title: 日本補綴歯科学会誌 Volume: 4 Pages: 353-363
  • NAID: 10031123456
• [Journal Article] Chemical analyses in dental adhesive technology (2012)
  • Author(s): Y. Yoshida
  • Journal Title: Jpn. Dent. Sci. Rev. Volume: 48 Issue: 2 Pages: 141-152
  • DOI: 10.1016/j.jdsr.2012.03.001
  • NAID: 10030957910
  • Peer Reviewed
• [Presentation] Phosphorylated pullulan bioadhesive for regeneration and reconstruction of bone and tooth (2012)
  • Author(s): Yoshida, Y., Okihara, T., Nakamura, M., Matsumoto, T
  • Organizer: 24◎<th>◎ Symposium and Annual Meeting of the International Society for Ceramics in Medicine
  • Place of Presentation: Fukuoka, Japan
• [Book] Basics in adhesion technology: In Caries management - Science and Clinical Practice. (Meyer-Luckel, H., Paris, S., Ekstrand, K. Ed.)(Chapter 14) (2013)
  • Author(s): Van Meerbeek, B., Yoshida, Y
  • Publisher: Thieme Medical Publishers, Inc., Stuttgart, Germany
• [Book] Phosphorylated pullulan bioadhesive for regeneration and reconstruction of bone and tooth. Key Engineering Materials (2013)
  • Author(s): Yoshida, Y., Okihara, T., Nakamura, M., Matsumoto, T
• [Book] Key Engineering Materials Visible Light-Induced Crosslinkable Gelatin for Direct Pulp Capping (2013)
  • Author(s): Nakamura, M., Yoshida, Y., Ito, Y
• [Book] 第6部製品種別ごとのデータ・情報の取得とまとめ方のポイント.第26章再生医療製品,再生医療用基材における留意点.医薬品・医療機器承認取得のためのデータ・情報の取得とまとめ方
  • Author(s): 伊藤義浩, 吉田靖弘
  • Publisher: 株式会社技術情報協会, 東京(in press)