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

• Project/Area Number: 15H04758
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kumamoto 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: ¥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)
• Keywords: DDS / 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.

Research Products

• [Journal Article] Dual therapeutic effects of an albumin-based nitric oxide donor on two experimental models of chronic kidney disease (2018)
  • 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
  • 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
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism (2017)
  • 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
  • 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 approach (2017)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Potential therapeutic interventions for chronic kidney disease-associated sarcopenia via indoxyl sulfate-induced mitochondrial dysfunction (2017)
  • 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
  • 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 disease (2016)
  • 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
  • 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-1 (2016)
  • 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
  • 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 properties (2016)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters (2016)
  • 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
  • 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 Injection (2015)
  • 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
  • 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 liposomes (2015)
  • 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
  • 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 Thrombocytopenia (2015)
  • 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
  • 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
  • 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
  • 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 Model (2015)
  • 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
  • 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 drugs (2015)
  • 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
  • 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 models (2015)
  • 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
  • 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 oxide (2015)
  • 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
  • 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
• [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
• [Presentation] Systemic effects of long-acting albumin-thioredoxin fusion protein against distant organ injury following AKI (2017)
  • Author(s): Nishida Kento, Watanabe Hiroshi, Fukagawa Masafumi, Maruyama Toru
  • Organizer: 米国腎臓学会議 Kidney Week-ASN 2017
• [Presentation] Long-acting albumin-thioredoxin fusion protein prevents AKI-associated acute lung injury (2016)
  • 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
  • Int'l Joint Research
• [Presentation] Downregulation of ABCG2, a Urate Exporter, by Parathyroid Hormone Enhances Urate Accumulation in Secondary Hyperparathyroidism (2016)
  • 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
  • Int'l Joint Research
• [Presentation] Molecular mechanism of uremic toxin induced-skeletal muscle atrophy in chronic kidney disease (2016)
  • 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
  • Int'l Joint Research
• [Presentation] Therapeutic application of a new type of nano-sized carbon monoxide donor in colitis model mice (2016)
  • 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
  • Int'l Joint Research
• [Presentation] S-Nitrosated human serum albumin dimer as a novel nano EPR enhancer applied to nanotechnology based anticancer drug (2016)
  • 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
  • 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
  • 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
• [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
• [Presentation] Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdommyolysis-associated acute kidney injury (2015)
  • 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
  • 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