Development of novel platform for injectable in vivo drug delivery system

• Project/Area Number: 24790052
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: ASAI Daisuke 聖マリアンナ医科大学, 医学部, 助教 (10423485)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ドラッグデリバリー / ハイドロゲル / 生分解材料 / ポリペプチド / 薬物デポ / インジェクタブルポリマー / ペプチド / 温度応答性高分子 / ドラッグデリバリーシステム / バイオマテリアル / 遺伝子工学 / 生体吸収性高分子 / ペプチド医薬 / ペプチド送達 / バイオレオロジー / 徐放

Research Abstract

The final goal of our study is: (1) to discover the seeds of next-generation biomedicine for infectious disease and cancer therapy; (2) to develop biocompatible materials for supporting surgical treatment. In this study, we focused elastin protein which expresses universally as an elastic fiber of vertebrates. We carried out the rational design and recombinant synthesis of thermally responsive peptide polymer-based hydrogels composed of an elastin-like polypeptide that rapidly forms a reversibly cross-linked hydrogel by the formation of intermolecular mild oxidative cross-links. We showed the utility of the hydrogels for the sustained release of medicines and the ability as to be an injectable and biodegradable material. These materials will find useful application in drug delivery and tissue engineering.

Research Products

• [Journal Article] Peptide substrates for G protein-coupled receptor kinase 2 (2014)
  • Author(s): D. Asai, R. Toita, M. Murata, Y. Katayama, H. Nakashima, J.H. Kang
  • Journal Title: FEBS Lett. Volume: Vol.588 Issue: 13 Pages: 2129-2132
  • DOI: 10.1016/j.febslet.2014.04.038
  • Peer Reviewed / Open Access
• [Journal Article] Liver cell-specific peptides derived from the PreS1 domain of human hepatitis B virus (2014)
  • Author(s): J.H. Kang, R. Toita, D. Asai, T. Yamaoka, M. Murata
  • Journal Title: J Virol Methods Volume: Vol.201 Pages: 20-23
  • DOI: 10.1016/j.jviromet.2014.02.013
  • Peer Reviewed
• [Journal Article] Protein polymer hydrogels by in situ, rapid and reversible self-gelation (2012)
  • Author(s): Asai, D., Xu, D., Liu, W., Garcia Quiroz, F., Callahan, D.J., Zalutsky, M.R., Craig, S.L., and Chilkoti, A
  • Journal Title: Biomaterials Volume: 33 Issue: 21 Pages: 5451-5458
  • DOI: 10.1016/j.biomaterials.2012.03.083
  • Peer Reviewed
• [Journal Article] Rheological properties of cysteine-containing elastin-like polypeptides solution and hydrogels (2012)
  • Author(s): Xu, D., Asai, D., Chilkoti, A., and Craig, S.L
  • Journal Title: Biomacromolecules Volume: 13 Issue: 8 Pages: 2315-2321
  • DOI: 10.1021/bm300760s
  • Peer Reviewed
• [Journal Article] Brachytherapy using injectable seeds that are self-assembled from genetically encoded polypeptide in situ (2012)
  • Author(s): Liu, W., McDaniel, J.R., Li, X., Asai, D., Garcia Quiroz, F., Schaal, J., Park, J.S., Zalutsky, M.R., and Chilkoti, A
  • Journal Title: Cancer Res Volume: 72 Pages: 5956-5965
  • Peer Reviewed
• [Presentation] 新規合成KSP阻害剤の抗腫瘍効果に関する研究 (2013)
  • Author(s): 武永美津子、竹内智紀、都倉享恵、濱口明美、太田有紀、浅井大輔、大石真也、中島秀喜、藤井信孝
  • Organizer: 第29回日本DDS学会学術集会
  • Place of Presentation: 京都
• [Presentation] Preparation of cancer-signal-responsive gene carrier via native chemical ligation (2013)
  • Author(s): Funamoto, D., Mori, T., Asai, D., Niidome, T., and Katayama, Y
  • Organizer: 4th Asian Biomaterials Congress
  • Place of Presentation: Hong Kong, China
• [Presentation] ネイティブケミカルライゲーションによるがん増殖シグナル応答性遺伝子キャリアの作製 (2013)
  • Author(s): 船本大起、森健、浅井大輔、新留琢郎、片山佳樹
  • Organizer: 第62回高分子学会年次大会
  • Place of Presentation: 京都
• [Presentation] ネイティブケミカルライゲーションによる癌増殖シグナル応答性遺伝子キャリアの作製 (2013)
  • Author(s): 船本大起、森健、浅井大輔、新留琢郎、片山佳樹
  • Organizer: 第６２回高分子学会
  • Place of Presentation: 京都国際会館, 京都市左京区
• [Presentation] Preparation of cancer-signal-responsive gene carrier via native chemical ligation (2013)
  • Author(s): Funamot D, Mori T, Asai D, Niidome T, and Katayama Y
  • Organizer: 4th Asian Biomaterials Congresss
  • Place of Presentation: Hong Kong University of Science and Technology, Hong Kong, China
• [Presentation] 新規合成KSP阻害剤の抗腫瘍効果に関する研究 (2013)
  • Author(s): 武永美津子、竹内智紀、都倉享恵、濱口明美、太田有紀、浅井大輔、大石真也、中島秀喜、藤井信孝
  • Organizer: 第２９回日本DDS学会学術集会
  • Place of Presentation: 京都テルサ, 京都市南区
• [Presentation] 次世代医用材料の開発 : 薬物徐放のための生体吸収性注射ゲル (2012)
  • Author(s): 浅井大輔、金本大成、福田靖、寺久保繁美、諸熊一則、柴山恵吾、中島秀喜
  • Organizer: 第72回神奈川県感染症医学会
  • Place of Presentation: 横浜
  • Year and Date: 2012-09-08
• [Presentation] 薬物デポを指向した人工蛋白質性注射ゲルの合理的設計 (2012)
  • Author(s): 浅井大輔、中島秀喜、Ashutosh Chilkoti
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] 人工エラスチンポリペプチドゲルの薬物徐放性の解析 (2012)
  • Author(s): 浅井大輔、中島秀喜、Ashutosh Chilkoti
  • Organizer: 日本バイオマテリアル学会シンポジウム2012
  • Place of Presentation: 仙台
• [Presentation] インジェクタブルDDSを実現する人工エラスチンポリペプチドゲル (2012)
  • Author(s): 浅井大輔、中島秀喜、Ashutosh Chilkoti
  • Organizer: 第28回日本DDS学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Thermally-responsive Elastin-like polypeptide engineered to locally deliver radionuclide payload leads to complete regression of solid tumor (2012)
  • Author(s): Liu, W., McDaniel, J.R., Li, X., Asai, D., Zalutsky, M.R., and Chilkoti, A
  • Organizer: 9th World Biomaterials Congress
  • Place of Presentation: Chengdu, China
• [Presentation] 遺伝子工学を用いた人工プロテインポリマーハイドロゲル (2012)
  • Author(s): 浅井大輔、中島秀喜、Ashutosh Chilkoti
  • Organizer: 第61回高分子学会年次大会
  • Place of Presentation: 横浜
• [Presentation] Preclinical studies on tumor retention, antitumor efficacy and toxicity of thermally responsive polypeptide-based radionuclide intratumoral depot in nude mice (2012)
  • Author(s): Liu, W., McDaniel, J.R., Li, X., Asai, D., Zalutsky, M.R., and Chilkoti, A
  • Organizer: American Association for Cancer Research Annual Meeting 2012
  • Place of Presentation: Chicago, IL, USA
• [Presentation] Thermally-responsive Elastin-like Polypeptide Engineered to Locally Deliver Radionuclide Payload Leads to Complete Regression of Solid Tumor (2012)
  • Author(s): Liw W et al.
  • Organizer: 9th World Biomaterials Congress
  • Place of Presentation: Chengdu, China
• [Presentation] インジェクタブルDDSを実現する人工エラスチンポリペプチドゲル (2012)
  • Author(s): 浅井大輔 ほか
  • Organizer: 第２８回日本ＤＤＳ学会学術集会
  • Place of Presentation: 札幌
• [Presentation] 薬物デポを指向した人工蛋白質性注射ゲルの合理的設計 (2012)
  • Author(s): 浅井大輔 ほか
  • Organizer: 第８５回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] 次世代医用材料の開発：薬物徐放のための生体吸収性注射ゲル
  • Author(s): 浅井大輔 ほか
  • Organizer: 第７２回神奈川県感染症医学会
  • Place of Presentation: 横浜
• [Remarks] 教室ホームページ(生体材料学研究)
  • URL: http://www.marianna-u.ac.jp/microbiology/office/003334.html
• [Remarks] 生体材料学研究（聖マリアンナ医科大学微生物学教室）
  • URL: http://www.marianna-u.ac.jp/microbiology/office/003334.html
• [Remarks] 生体材料学研究（聖マリアンナ医科大学微生物学教室）
  • URL: http://www.marianna-u.ac.jp/microbiology/office/003334.html