Innovation of a novel technology for supporting the development of DDS drugs and protein medicines by controling their pharmacokinetics.

• Project/Area Number: 24659021
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: OKU NAOTO 静岡県立大学, 薬学部, 教授 (10167322)
• Co-Investigator(Kenkyū-buntansha): ASAI Tomohiro 静岡県立大学, 薬学部, 准教授 (00381731) ; SHIMIZU Kosuke 静岡県立大学, 薬学部, 助教 (30423841)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 薬学 / 長期血中滞留性 / 薬物送達システム / リポソーム / ファージディスプレイペプチドライブラリー / バイオパニング / ドラッグデリバリー / ＤＤＳ

Research Abstract

In the development of drug nanocarriers in drug delivery systems or recombinant protein medicines, rapid blood clearance of these is frequently problematic. To overcome this rapid clearance, we attemped to obtain petides having long circulating characteristic by use of phage-displayed peptide library that presenting 5 mer random peptides. After intravenous injection of the library, we selected long circulating phages and identified long circulating peptides. Unfortunately, the circulating characteristics of drug nanocarriers was not improved by modifying the surface of them with the peptides. However, since cloned phages presenting these peptids showed quite long circulation in the bloodsteam of mice, we believe that these peptides are useful for the development of DDS drugs or protein drugs.

Research Products

• [Journal Article] Enhanced active targeting via cooperative binding of ligands on liposomes to target receptors (2013)
  • Author(s): Sugiyama T, Asai T, Nedachi YM, Katanasaka Y, Shimizu K, Maeda N, Oku N
  • Journal Title: PLoS One Volume: 8
• [Journal Article] Enhanced active targeting via cooperative binding of ligands on liposomes to target receptors. (2013)
  • Author(s): Sugiyama T, Asai T, Nedachi YM, Katanasaka Y, Shimizu K, Maeda N, Oku N.
  • Journal Title: PLoS One. Volume: 8 Issue: 6 Pages: e67550-e67550
  • DOI: 10.1371/journal.pone.0067550
  • Peer Reviewed
• [Journal Article] Systemic delivery of small interfering RNA by use of targeted polycation liposomes for cancer therapy. (2013)
  • Author(s): Kenjo E, Asai T, Yonenaga N, Ando H, Ishii T, Hatanaka K, Shimizu K, Urita Y, Dewa T, Nango M, Tsukada H, Oku N.
  • Journal Title: Biol Pharm Bull. Volume: 36 Pages: 287-291
  • NAID: 130003361373
• [Journal Article] Size-dependent induction of accelerated blood clearance phenomenon by repeated injections of polymeric micelles (2012)
  • Author(s): Koide H, Asai T, Kato H, Ando H, Shiraishi K,Yokoyama M, Oku N
  • Journal Title: Int J Pharm Volume: 432 Pages: 75-79
• [Journal Article] Size-dependent induction of accelerated blood clearance phenomenon by repeated injections of polymeric micelles (2012)
  • Author(s): H. Koide, T. Asai, H. Ando, K. Shiraishi,M. Yokoyama, and N. Oku
  • Journal Title: International Journal of Pharmaceutics Volume: 432 Issue: 1-2 Pages: 75-79
  • DOI: 10.1016/j.ijpharm.2012.04.049
  • Peer Reviewed
• [Presentation] Increased Half-life of secondly injected PEGylated liposomes in mice pretreated with doxorubicin-encapsulated PEGylated liposome (2013)
  • Author(s): Jantana Yahuafai, Tomohiro Asai, Genki Nakamura, Yuri Kiyokawa, Yoshihito Takeuchi, Kosuke Shimizu, Pongpun Siripong, Kenji Hyodo, Hiroshi Ishihara, Hiroshi Kikuchi, Naoto Oku
  • Organizer: International Liposome Society 2013 Meeting Liposome Advances : Progress in Drug and Vaccine Delivery
  • Place of Presentation: London, UK
  • Year and Date: 2013-12-14
• [Presentation] Enhanced circulation of secondly injected PEGylated liposomes after injection of doxorubicin-encapsulatd PEGylated liposomes (2013)
  • Author(s): Jantana Yahuafai, Yuri Kiyokawa, Yoshito Takeuchi, Daiki Saito, Kosuke Shimizu, Tomohiro Asai, Pongpun Siripong, Kenji Hyodo, Hiroshi Ishihara, Hiroshi Kikuchi, Naoto Oku
  • Organizer: The 5 th Conference
  • Place of Presentation: 名古屋
  • Year and Date: 2013-08-05
• [Presentation] ファージライブラリーを用いた長期血中滞留性ペプチドの探索 (2013)
  • Author(s): 清河友理、中田貴志、古屋恵一、清水広介、浅井知浩、奥直人
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [Presentation] Identification of a novel peptide targeting to human tumor vasculature for drug delivery (2012)
  • Author(s): Takashi Nakada, Koji Hirashima, Yuri Kiyokawa, Kentaro Hatanaka, Kosuke Shimizu, Tomohiro Asai, Nanoto Oku
  • Organizer: Liposome Research Days
  • Place of Presentation: Hangzou, China
  • Year and Date: 2012-10-09
• [Presentation] Identification of a novel peptide targeting to human tumor vasculature for drug delivery (2012)
  • Author(s): T Nakada, K Hirashima, Y Kiyokawa, K Hatanaka, K Shimizu, T Asai, N Oku
  • Organizer: Liposome Research Days 2012
  • Place of Presentation: Hangzhou, China
• [Presentation] Enhanced circulation of secondly injected PEGylated liposomes after injection of doxorubicin-encapsulatd PEGylated liposomes
  • Author(s): Jantana Yahuafai, Yuri Kiyokawa, Yoshito Takeuchi, Daiki Saito, Kosuke Shimizu, Tomohiro Asai, Pongpun Siripong, Kenji Hyodo, Hiroshi Ishihara, Hiroshi Kikuchi, Naoto Oku
  • Organizer: The 5th Asian Arden Conference
  • Place of Presentation: 名古屋
• [Presentation] Increased Half-life of secondly injected PEGylated liposomes in mice pretreated with doxorubicin-encapsulated PEGylated liposomes
  • Author(s): Jantana Yafuafai, Tomohiro Asai, Genki Nakamura, Yuri Kiyokawa, Yoshihito Takeuchi, Kosuke Shimizu, Pongpun Siripong, Kenji Hyodo, Hiroshi Ishihara, Hiroshi Kikuchi, Naoto Oku
  • Organizer: International Liposome Society 2013 Meeting
  • Place of Presentation: London UK
• [Remarks]
  • URL: http://w3pharm.u-shizuoka-ken.ac.jp/radiobio/mbc/Home.html