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Development of albumin DDS carrier based on an understanding of the endogenous albumin transport system

Research Project

Project/Area Number 21H02645
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionKyoto Pharmaceutical University (2023)
The University of Tokushima (2021-2022)

Principal Investigator

Ishima Yu  京都薬科大学, 薬学部, 教授 (00457590)

Co-Investigator(Kenkyū-buntansha) 小田切 優樹  崇城大学, 薬学部, 特任教授 (80120145)
石田 竜弘  徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (50325271)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywordsアルブミン / ドラッグデリバリー / アルブミン受容体 / ストレス / がん治療 / ワクチン / ドラッグデリバリーシステム / アクティブターゲティング
Outline of Research at the Start

ヒトの血中にもっとも多量に存在するアルブミンは、脂肪酸などの多様な化合物の運搬体として機能しているが、どのように各化合物をそれぞれの臓器へ選択的に送達させているのかは不明であった。近年、生体の各臓器には、多様なアルブミン受容体が発現しており、そのアルブミンに対する認識性には違いがあることが報告された。我々は、この様々な種類のアルブミン受容体のアルブミン認識性を明らかにすることにより、様々な組織移行性をもつアルブミンの開発が出来ると考え、本研究課題である「内因的アルブミン輸送システムの理解に基づく革新的アルブミンドラッグデリバリーシステム(DDS)キャリアの構築」に着手する。

Outline of Final Research Achievements

In human body, various albumin receptors are expressed in each organ, and their recognition of difference part in albumin. We started this research project with the idea that by clarifying the albumin recognition of these albumin receptors, we may be able to develop albumins with various tissue migration properties. As a result, it was revealed that when various stresses were applied to albumin, albumin changed structure into three patterns, and showed organ migration dependent on the pattern of structural change. For example, heat-treated albumin significantly increased its migration to the spleen, and acid-treated albumin acquired the property of accumulating specifically in cancer tissue. This result will lead to the development of vaccines and efficient cancer treatment in the future.

Academic Significance and Societal Importance of the Research Achievements

従来より薬物の生体内輸送を担っているアルブミンを基盤にして、変性や酸化、化学的修飾を人為的に導入する臓器ターゲッティング能を付与する技術は、これまでにない研究成果である。特に学術的な意義は、変性や酸化、あるいは化学的修飾を人為的に導入したアルブミンの体内動態を解明することで、各組織のアルブミン認識性の理解が深まり、組織網羅的なデータ収集を行うことでドラッグデリバリー研究に大いに貢献できると考える。また社会的意義として、本研究成果に基づく製剤開発は、様々な薬の組織選択的移行性を高めることから、副作用の少ない安全な薬物治療が可能になり、使用する薬剤の投与量の削減による医療経済的効果も期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (45 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (17 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 17 results,  Open Access: 10 results) Presentation (25 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Remarks (1 results)

  • [Int'l Joint Research] Curtin University(オーストラリア)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Monash University Malaysia/International Medical University(マレーシア)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Characterization of Supersulfide in Serum Albumin and Its Therapeutic Application2024

    • Author(s)
      Ikeda Mayumi、Fukuta Tatsuya、Iwao Yasunori、Otagiri Masaki、Maruyama Toru、Ishida Tatsuhiro、Ishima Yu
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 144 Issue: 1 Pages: 51-56

    • DOI

      10.1248/yakushi.23-00162-3

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2024-01-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute Kidney Injury Caused by Rhabdomyolysis Is Ameliorated by Serum Albumin-Based Supersulfide Donors through Antioxidative Pathways2024

    • Author(s)
      Ikeda-Imafuku Mayumi、Fukuta Tatsuya、Tuan Giam Chuang Victor、Sawa Tomohiro、Maruyama Toru、Otagiri Masaki、Ishida Tatsuhiro、Ishima Yu
    • Journal Title

      Pharmaceuticals

      Volume: 17 Issue: 1 Pages: 128-128

    • DOI

      10.3390/ph17010128

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The binding selectivity of quercetin and its structure-related polyphenols to human serum albumin using a fluorescent dye cocktail for multiplex drug-site mapping2024

    • Author(s)
      Mukai Rie、Okuyama Hitomi、Uchimura Miku、Sakao Kozue、Matsuhiro Miyu、Ikeda-Imafuku Mayumi、Ishima Yu、Nishikawa Miyu、Ikushiro Shinichi、Tai Akihiro
    • Journal Title

      Bioorganic Chemistry

      Volume: 145 Pages: 107184-107184

    • DOI

      10.1016/j.bioorg.2024.107184

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of Albumin-Fused Thioredoxin against 6-Hydroxydopamine-Induced Neurotoxicity In Vitro2023

    • Author(s)
      Sakakibara Okina、Shimoda Mikako、Yamamoto Gaku、Higashi Youichirou、Ikeda-Imafuku Mayumi、Ishima Yu、Kawahara Masahiro、Tanaka Ken-ichiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 11 Pages: 9758-9758

    • DOI

      10.3390/ijms24119758

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-PEG IgM production induced by PEGylated liposomes as a function of administration route2023

    • Author(s)
      Takata Haruka、Shimizu Taro、Yamade Rina、Elsadek Nehal E.、Emam Sherif E.、Ando Hidenori、Ishima Yu、Ishida Tatsuhiro
    • Journal Title

      Journal of Controlled Release

      Volume: 360 Pages: 285-292

    • DOI

      10.1016/j.jconrel.2023.06.027

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticles for the Treatment of Hepatitis2023

    • Author(s)
      Yasuda K, Maeda H, Kinoshita R, Minayoshi Y, Mizuta Y, Nakamura Y, Imoto S, Nishi K, Yamasaki K, Sakuragi M, Nakamura T, Ikeda-Imafuku M, Iwao Y, Ishima Y, Ishida T, Iwakiri Y, Otagiri M, Watanabe H, Maruyama T
    • Journal Title

      ACS Nano

      Volume: 17 Issue: 17 Pages: 16668-16681

    • DOI

      10.1021/acsnano.3c02877

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Maleimide-Terminally Modified PEGylated Liposome Induced the Accelerated Blood Clearance Independent of the Production of Anti-PEG IgM Antibodies2022

    • Author(s)
      Ishima Yu、Yamazaki Nio、Chuang Victor T. G.、Shimizu Taro、Ando Hidenori、Ishida Tatsuhiro
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 45 Issue: 10 Pages: 1518-1524

    • DOI

      10.1248/bpb.b22-00389

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2022-10-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The New Delivery Strategy of Albumin Carrier Utilizing the Interaction with Albumin Receptors2022

    • Author(s)
      Ishima Yu、Maruyama Toru、Otagiri Masaki、Chuang Victor T. G.、Ishida Tatsuhiro
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 70 Issue: 5 Pages: 330-333

    • DOI

      10.1248/cpb.c21-01024

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2022-05-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel nitric oxide donor, nitrated phenylbutyrate, induces cell death of human pancreatic cancer cells and suppresses tumor growth of cancer xenografts2022

    • Author(s)
      Beppu Takuro、Nishi Koji、Imoto Shuhei、Araki Waka、Setoguchi Itaru、Ueda Ayaka、Suetsugi Naho、Ishima Yu、Ikeda Tokunori、Otagiri Masaki、Yamasaki Keishi
    • Journal Title

      Oncology Reports

      Volume: 48 Issue: 4 Pages: 178-178

    • DOI

      10.3892/or.2022.8393

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Nitrated Form of Nateglinide Induces Apoptosis in Human Pancreatic Cancer Cells Through a Caspase-dependent Mechanism.2022

    • Author(s)
      Nishi K, Imoto S, Beppu T, Uchibori S, Yano A, Ishima YU, Ikeda T, Tsukigawa K, Otagiri M, Yamasaki K.
    • Journal Title

      Anticancer Res.

      Volume: 42 Issue: 3 Pages: 1333-1338

    • DOI

      10.21873/anticanres.15601

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A mouse model for studying the effect of blood anti-PEG IgMs levels on the in vivo fate of PEGylated liposomes2022

    • Author(s)
      Marwa M. El Sayed, Taro Shimizu, Amr S. Abu Lila, Nehal E. Elsadek, Sherif E. Emam, Eman Alaaeldin, Amal Kamal, Hatem A. Sarhan, Hidenori Ando, Yu Ishima, Tatsuhiro Ishida
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 615 Pages: 121539-121539

    • DOI

      10.1016/j.ijpharm.2022.121539

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Subvisible Particles Derived by Dropping Stress Enhance Anti-PEG Antibody Production and Clearance of PEGylated Proteins in Mice2022

    • Author(s)
      Nakajima Takaki、Nagano Kazuya、Fukuda Yuka、Ishima Yu、Shibata Hiroko、Isaka Ryo、Zhang Tian-qi、Haga Yuya、Higashisaka Kazuma、Tsujino Hirofumi、Ishida Tatsuhiro、Ishii-Watabe Akiko、Tsutsumi Yasuo
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 111 Issue: 5 Pages: 1363-1369

    • DOI

      10.1016/j.xphs.2022.01.023

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 8‐Prenylnaringenin tissue distribution and pharmacokinetics in mice and its binding to human serum albumin and cellular uptake in human embryonic kidney cells2022

    • Author(s)
      Tanaka Yoshiaki、Okuyama Hitomi、Nishikawa Miyu、Ikushiro Shin‐ichi、Ikeda Mayumi、Ishima Yu、Ukawa Yuichi、Oe Kenichi、Terao Junji、Mukai Rie
    • Journal Title

      Food Science & Nutrition

      Volume: 10 Issue: 4 Pages: 1070-1080

    • DOI

      10.1002/fsn3.2733

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH.2022

    • Author(s)
      Sonoda K, Wakayama T, Kinoshita M, Shuto T, Kai H, Tanaka M, Sasaki Y, Iwakiri Y, Otagiri M
    • Journal Title

      J Control Release

      Volume: 341 Pages: 457-474

    • DOI

      10.1016/j.jconrel.2021.11.039

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evidence for Delivery of Abraxane via a Denatured-Albumin Transport System2021

    • Author(s)
      Hama Maichi、Ishima Yu、Chuang Victor Tuan Giam、Ando Hidenori、Shimizu Taro、Ishida Tatsuhiro
    • Journal Title

      ACS Applied Materials & Interfaces

      Volume: 13 Issue: 17 Pages: 19736-19744

    • DOI

      10.1021/acsami.1c03065

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Therapeutic Effect of Human Serum Albumin Dimer-Doxorubicin Complex against Human Pancreatic Tumors.2021

    • Author(s)
      Kinoshita R, Ishima Y, Chuang VTG, Watanabe H, Shimizu T, Ando H, Okuhira K, Otagiri M, Ishida T, Maruyama T
    • Journal Title

      Pharmaceutics.

      Volume: 13 Issue: 8 Pages: 1209-1209

    • DOI

      10.3390/pharmaceutics13081209

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduction-responsive and multi-drug deliverable albumin nanoparticles: an antitumor drug to Abraxane_ against human pancreatic tumor-bearing mice2021

    • Author(s)
      Naoki Hirakawa, Yu Ishima, Ryo Kinoshita, Ryuto Nakano, Victor Tuan Giam Chuang, Hidenori Ando, Taro Shimizu, Keiichiro Okuhira, Toru Maruyama, Masaki Otagiri, Tatsuhiro Ishida
    • Journal Title

      ACS Applied Bio Materials

      Volume: 268 Issue: 5 Pages: 4302-4309

    • DOI

      10.1021/acsabm.1c00110

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 内因性タンパク質の超硫黄化とその生理的意義の解明2023

    • Author(s)
      異島 優
    • Organizer
      アルブミン研究会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 様々な生体分子の生理機能における超硫黄分子の役割2023

    • Author(s)
      異島 優
    • Organizer
      生物科学フロンティアセミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 簡便な超硫黄分子測定系を用いた生化学への新たなアプローチ2023

    • Author(s)
      異島 優
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] LPS誘発敗血症モテルに対する ヒト血清アルフミンの保護効果におけるCystathionine β-synthaseの関与2023

    • Author(s)
      異島 優 、向井 愛菜、石田 竜弘
    • Organizer
      第76回日本酸化ストレス学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Differential organ-specific distribution of human serum albumin denatured by various modifications2022

    • Author(s)
      橋本 愛子、異島 優、安藤 英紀、清水 太郎、石田 竜弘
    • Organizer
      15th International Symposium on Nanomedicine
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biological roles of supersulfide in human hair2022

    • Author(s)
      平井 傑琉、田坂 菜々美、安藤 英紀、清水 太郎、石田 竜弘、異島 優
    • Organizer
      Redox Week in Sendai 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The EPR effect and beyond: Drug delivery for refractory cancer therapy via an Endogenous Albumin Transport system2022

    • Author(s)
      異島 優、丸山 徹、赤池 孝章、小田切 優樹、石田 竜弘
    • Organizer
      Redox Week in Sendai 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 超硫黄分子のレドックス制御機構の解明と抗酸化剤への応用2022

    • Author(s)
      池田 真由美、異島 優、丸山 徹、小田切 優樹、石田 竜弘
    • Organizer
      第30回DDSカンファランス
    • Related Report
      2022 Annual Research Report
  • [Presentation] 難水溶性薬物に対する溶解補助及び動態改善を企図した新規アルブミンナノ粒子の有用性評価2022

    • Author(s)
      中野 琉人、平川 尚樹、安藤 英紀、清水 太郎、石田 竜弘、異島 優
    • Organizer
      日本薬剤学会第3回超分子薬剤学FGシンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] 様々な生体液に含まれる超硫黄分子の生理的意義の解明2022

    • Author(s)
      異島 優、池田 真由美、酒井 真紀、長船 裕輝、岩尾 康範、丸山 徹、小田切 優樹、石田 竜弘
    • Organizer
      フォーラム2022:衛生薬学・環境トキシコロジー
    • Related Report
      2022 Annual Research Report
  • [Presentation] 毛髪中に含まれる超硫黄分子の検出および機能解明2022

    • Author(s)
      平井 傑琉、清水 太郎、安藤 英紀、石田 竜弘、異島 優
    • Organizer
      フォーラム2022:衛生薬学・環境トキシコロジー
    • Related Report
      2022 Annual Research Report
  • [Presentation] スルホサリチル酸を用いた新規アルブミンナノ粒子化法の開発と敗血症への応用2022

    • Author(s)
      十鳥 有希菜、平川 尚樹、木下 遼、清水 太郎、安藤 英紀、石田 竜弘、異島 優
    • Organizer
      第49回日本毒性学会学術年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒト血清アルブミンナノ粒子(HSAnp)を利用したDDSの新規開発とがんワクチンへの展開2022

    • Author(s)
      山出 莉奈、清水 太郎、平川 尚樹、安藤 英紀、異島 優、石田 竜弘
    • Organizer
      第38回日本DDS学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] アルブミンを基盤とした臓器特異的移行性を有するDDSキャリアの作製2022

    • Author(s)
      橋本 愛子、異島 優、安藤 英紀、石田 竜弘
    • Organizer
      第38回日本DDS学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] アルブミンの体内動態特性に基づくDDSキャリアの開発に関する研究2022

    • Author(s)
      異島 優
    • Organizer
      日本薬剤学会第37年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] アルブミン結合型パクリタキセル製剤Abraxaneの変性アルブミン受容体を介した薬物輸送メカニズム2021

    • Author(s)
      濵眞壱、異島優、安藤英紀、清水太郎、石田竜弘
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] PEG修飾タンパクの凝集体形成が及ぼす抗PEG抗体産生・血中滞留性への影響2021

    • Author(s)
      福田悠花、中島祟樹、異島優、安藤英紀、清水太郎、長野一也、柴田寛子、石田竜弘
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 効率的な体液性免疫誘導に向けたアルブミンナノキャリアの開発2021

    • Author(s)
      山出莉奈、平川尚樹、清水太郎、安藤英紀、異島優、石田竜弘
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 致死性エンドトキシンショックに対するヒト血清アルブミンの治療効果の機序解明2021

    • Author(s)
      向井愛菜、異島優、安藤英紀、清水太郎、石田竜弘
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 様々なヒト血清アルブミン受容体を介した薬物キャリアの開発2021

    • Author(s)
      橋本愛子、濱眞壱、異島優、安藤英紀、清水太郎、石田竜弘
    • Organizer
      日本薬剤学会第36年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 活性イオウ付加型ヒト血清アルブミンの腫瘍への送達は小疱形成を介した細胞死を誘導する2021

    • Author(s)
      松尾菜々、異島優、安藤英紀、清水太郎、石田竜弘
    • Organizer
      第29回DDSカンファランス
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高い抗体産生誘導能を有する抗原搭載アルブミンナノ粒子の開発2021

    • Author(s)
      山出莉奈、平川尚樹、清水太郎、安藤英紀、異島優、石田竜弘
    • Organizer
      日本薬剤学会第2回超分子薬剤学FGシンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 活性硫黄化が織りなすタンパク質の新たな生体防御機構2021

    • Author(s)
      異島優
    • Organizer
      第28回日本血液代替物学会年次大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] アルブミンを基盤とした臓器特異的移行性を有するDDSキャリアの作製2021

    • Author(s)
      橋本愛子、異島優、安藤英紀、清水太郎、石田竜弘
    • Organizer
      第15回次世代を担う若手のための医療薬科学シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] Sulfane sulfur付加型HSAを用いた還元ストレス誘導を介するがん治療戦略2021

    • Author(s)
      松尾菜々、異島優、安藤英紀、清水太郎、石田竜弘
    • Organizer
      第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
    • Related Report
      2021 Annual Research Report
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    • URL

      https://www.tokushima-u.ac.jp/ph/faculty/labo/ykz/

    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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