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Development of renal delivery system for hybridized tissue regenerating factors and its application for kidney disease

Research Project

Project/Area Number 15H04758
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionKumamoto University

Principal Investigator

MARUYAMA TORU  熊本大学, 薬学部, 教授 (90423657)

Co-Investigator(Kenkyū-buntansha) 渡邊 博志  熊本大学, 薬学部, 准教授 (70398220)
異島 優  熊本大学, 薬学部, 助教 (00457590)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
KeywordsDDS / アルブミン / ドラッグデリバリー / ドラックデリバリー
Outline of Final Research Achievements

In this study, we successfully created the innovative nano-sized carrier which possessed both the superior blood circulation and the efficient delivery to kidney by the associations of peptide that specifically recognized kidneys to human albumin (HSA). Then, kidney regeneration and repair factors were loaded to HSA by the albumin engineering technology established by us. This hybrid-albumin DDS showed efficient and sustained delivery of regeneration and repair factors to the kidneys, even though under the chronic renal failures. Consequently, hybrid-albumin DDS showed excellent renoprotective and anti-fibrotic actions against chronic renal failure model animals. Since hybrid-albumin DDS is a cell-free and self-inducing regenerating system, it can be possible to conduct early intervention to the injured kidneys, and substantially lead to repair and regenerate kidneys. Thus, the hybrid system can be expected as a novel pre-emptive Medicine using Self-Repairing potential.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (32 results)

All 2018 2017 2016 2015

All Journal Article (19 results) (of which Int'l Joint Research: 19 results,  Peer Reviewed: 19 results,  Open Access: 7 results) Presentation (13 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Journal Article] Dual therapeutic effects of an albumin-based nitric oxide donor on two experimental models of chronic kidney disease2018

    • Author(s)
      Oshiro S, Ishima Y, Maeda H, Honda N, Bi J, Kinoshita R, Ikeda M, Iwao Y, Imafuku T, Nishida K, Miyamura S, Watanabe H, Otagiri M, Maruyama T
    • Journal Title

      J Pharm Sci

      Volume: 107 Issue: 3 Pages: 848-855

    • DOI

      10.1016/j.xphs.2017.10.023

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A novel S-sulfhydrated human serum albumin preparation suppresses melanin synthesis,2018

    • Author(s)
      Ikeda M, Ishima Y, Kinoshita R, Chuang VTG, Tasaka N, Matsuo N, Watanabe H, Shimizu T, Ishida T, Otagiri M, Maruyama T,
    • Journal Title

      Redox Biology

      Volume: 14 Pages: 354-360

    • DOI

      10.1016/j.redox.2017.10.007

    • NAID

      120007029979

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of EPR effect and albumin-protein interactions using S-Nitrosated Human Serum Albumin Dimer.2017

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

      Biomaterials.

      Volume: 140 Pages: 162-169

    • DOI

      10.1016/j.biomaterials.2017.06.021

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism2017

    • Author(s)
      Sugimoto R, Watanabe H, Ikegami K, Enoki Y, Imafuku T, Sakaguchi Y, Murata M, Nishida K, Miyamura M, Ishima Y, Tanaka M, Matsushita K, Komaba H, Fukagawa M, Otagiri M, Toru Maruyama
    • Journal Title

      Kidney Int

      Volume: 91 Issue: 3 Pages: 658-670

    • DOI

      10.1016/j.kint.2016.09.041

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quantitative determination of polysulfide in albumins, plasma proteins and biological fluid samples using a novel combined assays approach2017

    • Author(s)
      keda, M. Ishima, Y. Shibata, A. Chuang, V. T. G. Sawa, T. Ihara, H. Watanabe, H. Xian, M. Ouchi, Y. Shimizu, T. Ando, H. Ukawa, M. Ishida, T. Akaike, T. Otagiri, M. Maruyama, T.
    • Journal Title

      Analytica Chimica Acta

      Volume: 969 Pages: 18-25

    • DOI

      10.1016/j.aca.2017.03.027

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential therapeutic interventions for chronic kidney disease-associated sarcopenia via indoxyl sulfate-induced mitochondrial dysfunction2017

    • Author(s)
      Enoki Y, Watanabe H, Arake R, Fujimura R, Ishiodori K, , Imafuku T, Nishida T, Sugimoto R, Nagao S, Miyamura S, Ishima Y, Tanaka M, Matsushita K, Komaba H, Fukagawa M, Otagiri M, Maruyama T
    • Journal Title

      J Cachexia Sarcopenia Muscle

      Volume: 印刷中

    • NAID

      120006869527

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human Serum Albumin Hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease2016

    • Author(s)
      Shibata A, Ishima Y, Ikeda M, Sato H, Imafuku T, Chuang VTG, Ouchi Y, Abe T, Watanabe H, Ishida T, Otagiri M, Maruyama T
    • Journal Title

      Biochem Biophys Res Comm

      Volume: 479 Pages: 578-583

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-12016

    • Author(s)
      Enoki Y, Watanabe H, Arake R, Sugimoto R, Imafuku T, Tominaga Y, Ishima Y, Kotani S, Nakajima M, Tanaka M, Matsushita K, Fukagawa M, Otagiri M, Maruyama T
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 32084-32084

    • DOI

      10.1038/srep32084

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Carbon monoxide-bound hemoglobin-vesicles ameliorates multi-organ injuries induced by severe acute pancreatitis in mice via their anti-inflammatory and anti-oxidant properties2016

    • Author(s)
      Nagao S, Taguchi K, Sakai H, Yamasaki K, Watanabe H, Otagiri M, Maruyama T
    • Journal Title

      Int J Nanomedicine

      Volume: 11 Pages: 5611-5620

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters2016

    • Author(s)
      Yamada K, Yokomaku K, Haruki R, Taguchi K, Nagao S, Maruyama T, Otagiri M, Komatsu T
    • Journal Title

      PLoS One

      Volume: 19 Issue: 2 Pages: 1-12

    • DOI

      10.1371/journal.pone.0149526

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biological Responsiveness and Metabolic Performance of Liposome-Encapsulated Hemoglobin (Hemoglobin-Vesicles) in Apolipoprotein E-Deficient Mice after Massive Intravenous Injection2015

    • Author(s)
      Taguchi K, Nagao S, Yamasaki K, Sakai H, Seo H, Maruyama T, Otagiri M
    • Journal Title

      Biol Pharm Bull

      Volume: 38 Pages: 1606-16

    • NAID

      130005101572

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] S-Nitrosated human serum albumin dimer as novel nano EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes2015

    • Author(s)
      Kinoshita R, Ishima Y, Ikeda M, Kragh-Hansen U, Fang J, Nakamura H, Chuang VTG, Tanaka R, Maeda H, Kodama A, Watanabe H, Maeda H, Otagiri M, Maruyama T
    • Journal Title

      J Control Release

      Volume: 217 Pages: 1-9

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pharmacokinetic Properties of Single and Repeated Injection of Liposomal Platelet Substitute in a Rat Model of Red Blood Cell Transfusion-Induced Dilutional Thrombocytopenia2015

    • Author(s)
      Hashimoto M, Taguchi K, Ogaki S, Watanabe H, Kinoshita M, Nishikawa K, Takeoka S, Ikeda Y, Handa M, Otagiri M, Maruyama T
    • Journal Title

      J Pharm Sci

      Volume: 104 Pages: 3968-76

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute.2015

    • Author(s)
      Haruki R, Kimura T, Iwasaki H, Yamada K, Kamiyama I, Kohno M, Taguchi K, Nagao S, Maruyama T, Otagiri M, Komatsu T.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 12778-12778

    • DOI

      10.1038/srep12778

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury.2015

    • Author(s)
      Nishida K, Watanabe H, Ogaki S, Kodama A, Tanaka R, Imafuku T, Ishima Y, Giam Chuang VT, Toyoda M, Kondoh M, Wu Q, Fukagawa M, Otagiri M, Maruyama T.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 14471-14471

    • DOI

      10.1038/srep14471

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of Repeated Injections of Adenosine Diphosphate-Encapsulated Liposomes Coated with a Fibrinogen γ-Chain Dodecapeptide Developed as a Synthetic Platelet Substitute on Accelerated Blood Clearance in a Healthy and an Anticancer Drug-Induced Thrombocytopenia Rat Model2015

    • Author(s)
      Taguchi K, Hashimoto M, Ogaki S, Watanabe H, Takeoka S, Ikeda Y, Handa M, Otagiri M, Maruyama T
    • Journal Title

      J Pharm Sci

      Volume: 104 Pages: 3084-9

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cross-linked human serum albumin dimer has the potential for use as a plasma-retaining agent for the fatty acid-conjugated antidiabetic drugs2015

    • Author(s)
      Taguchi K, Chuang VT, Yamasaki K, Urata Y, Tanaka R, Anraku M, Seo H, Kawai K, Maruyama T, Komatsu T, Otagiri M
    • Journal Title

      J Pharm Pharmacol

      Volume: 67 Pages: 255-263

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Polythiol-containing, recombinant mannosylated-albumin is a superior CD68+/CD206+ Kupffer cell-targeted nano-antioxidant for the treatment of two acute hepatitis models2015

    • Author(s)
      Maeda H, Hirata K, Watanabe H, Ishima Y, Chuang VTG, Taguchi K, Inatsu A, Kinoshita M, Tanaka M, Sasaki Y, Otagiri M, Maruyama T
    • Journal Title

      J Pharm Exp Ther

      Volume: 352 Pages: 244-57

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Poly-S-nitrosated human albumin enhances the antitumor and antimetastasis effect of bevacizumab, partly by inhibiting autophagy via the generation of nitric oxide2015

    • Author(s)
      Ishima Y, Inoue A, Fang J, Kinoshita R, Ikeda M, Watanabe H, Maeda H, Otagiri M, Maruyama T
    • Journal Title

      Cancer Sci

      Volume: 106 Pages: 194-200

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] アルブミン融合技術を駆使した血中滞留型チオレドキシンの設計と急性腎障害及び腎-多臓器連関治療への展開2017

    • Author(s)
      西田健人
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 持続型BMP7誘導体の肝線維化モデルに対する有用性評価2017

    • Author(s)
      高野芽依、渡邊博志、前田仁志、小田切優樹、丸山徹
    • Organizer
      第34回日本薬学会九州支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Systemic effects of long-acting albumin-thioredoxin fusion protein against distant organ injury following AKI2017

    • Author(s)
      Nishida Kento, Watanabe Hiroshi, Fukagawa Masafumi, Maruyama Toru
    • Organizer
      米国腎臓学会議 Kidney Week-ASN 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Long-acting albumin-thioredoxin fusion protein prevents AKI-associated acute lung injury2016

    • Author(s)
      Kento Nishida, Hiroshi Watanabe, Masafumi Fukagawa and Toru Maruyama
    • Organizer
      第49回米国腎臓学会議 Kidney Week-ASN 2016
    • Place of Presentation
      USA:Chicago McCormick Place
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Downregulation of ABCG2, a Urate Exporter, by Parathyroid Hormone Enhances Urate Accumulation in Secondary Hyperparathyroidism2016

    • Author(s)
      Hiroshi Watanabe, Ryusei Sugimoto, Motoko Tanaka, Hirotaka Komaba, Masafumi Fukagawa and Toru Maruyama
    • Organizer
      第49回米国腎臓学会議 Kidney Week-ASN 2016
    • Place of Presentation
      USA:Chicago McCormick Place
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular mechanism of uremic toxin induced-skeletal muscle atrophy in chronic kidney disease2016

    • Author(s)
      Hiroshi Watanabe, Yuki Enoki, Riho Arake, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa and Toru Maruyama
    • Organizer
      The 2nd Asian Conference for Frailty and Sarcopenia
    • Place of Presentation
      Japan, Nagoya
    • Year and Date
      2016-11-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Therapeutic application of a new type of nano-sized carbon monoxide donor in colitis model mice2016

    • Author(s)
      Saori Nagao, Kazuaki Taguchi, Hiromi Sakai, Masaki Otagiri, Toru Maruyama
    • Organizer
      2016 Controlled Release Society Annual Meeting & Exposition
    • Place of Presentation
      Washington State Convention Center,USA
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] S-Nitrosated human serum albumin dimer as a novel nano EPR enhancer applied to nanotechnology based anticancer drug2016

    • Author(s)
      Ryo Kinoshita (D2), Yu Ishima, Mayumi Ikeda, Jun Fang, Hiroshi Maeda,Masaki Otagiri, Toru Maruyama
    • Organizer
      2016 Controlled Release Society Annual Meeting & Exposition
    • Place of Presentation
      Washington State Convention Center,USA
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アルブミン融合技術を利用した血中滞留型チオレドキシンの創製と難治性肺疾患治療への応用2015

    • Author(s)
      渡邊 博志、田中 遼大、異島 優、Chuang VTG、小田切 優樹、丸山 徹
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会合同大会ワークショップ
    • Place of Presentation
      兵庫:神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 腎指向型アルブミン-BMP7ハイブリット体の創製と腎保護効果の検討2015

    • Author(s)
      戸田 翔太、渡邊 博志、弥永 直樹、濱崎 慶輔、國安 明彦、長谷川 功紀、後藤 久美子、異島 優、小田切 優樹、丸山 徹
    • Organizer
      第32回 日本薬学会九州支部大会
    • Place of Presentation
      宮崎:九州保健福祉大学
    • Year and Date
      2015-11-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] アルブミン融合技術を利用した血中滞留型BMP7の作製と腎線維化抑制作用2015

    • Author(s)
      渡邊 博志、戸田 翔太、異島 優、小田切 優樹、丸山 徹
    • Organizer
      第30回日本薬物動態学会
    • Place of Presentation
      東京:タワーホール船堀
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdommyolysis-associated acute kidney injury2015

    • Author(s)
      Hiroshi Watanabe, Kento Nishida, Masafumi Fukagawa, Toru Maruyama
    • Organizer
      第48回米国腎臓学会議
    • Place of Presentation
      USA:San Diego Convention Center
    • Year and Date
      2015-11-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 遺伝子工学的手法を用いた血中滞留型BMP7の設計と持続的腎保護作用の評価2015

    • Author(s)
      戸田 翔太、渡邊 博志、異島 優、小田切 優樹、丸山 徹
    • Organizer
      第58回 日本腎臓学会学術総会
    • Place of Presentation
      愛知:名古屋国際会議場
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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