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Eye drop administration of recombinant serum lipoproteins for the treatment of age-related macular degeneration

Research Project

Project/Area Number 18K18460
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Studies on the Super-Aging Society
Research InstitutionToyama Prefectural University

Principal Investigator

Murakami Tatsuya  富山県立大学, 工学部, 教授 (90410737)

Co-Investigator(Kenkyū-buntansha) 池田 華子  京都大学, 医学研究科, 准教授 (20372162)
高田 耕児  富山県産業技術研究開発センター, その他部局等, 主任研究員 (40530621)
安田 佳織  富山県立大学, 工学部, 講師 (70707231)
Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords加齢黄斑変性 / 高密度リポタンパク質 / 点眼剤 / 点眼 / 薬物送達システム / リポタンパク質 / 治療用ナノ粒子 / ドラッグデリバリーシステム / 後眼部疾患 / ナノ粒子
Outline of Final Research Achievements

Toward the development of eye drops for the treatment of age-related macular degeneration using variants of high-density lipoprotein (HDL), we conducted research as described below.
After eye drop instillation of drug-loaded HDL variants to rats, the distribution of the drug in the posterior segment of the rat eyes (sclera, choroid, retina) and the vitreous body was investigated by LC-MS/MS. Drug concentrations were in the order of sclera > choroids > retina, and the drug were not detected in the vitreous body. These results suggest a trans-scleral route for the delivery for the drug by HDL variants to the posterior eye segment in rats.
A simple HDL preparation method that can be used for industrial production has been developed. By mixing an ethanol solution of HDL component lipid and a urea solution of HDL component protein and incubating the mixture at the phase transition temperature of the lipid membrane, HDL was obtained at a high yield comparable to that for the existing method.

Academic Significance and Societal Importance of the Research Achievements

加齢黄斑変性は加齢が最大のリスクファクターの難治疾患であり、我が国で第4番目の失明原因である(欧米では第1位)。現在の治療法(抗体医薬品の眼球内注射)は、患者への肉体的負担が大きく、また患者急増による医療従事者の労働負担も問題となっている。そしてもう1つの問題は、長期的にはこの治療法は有効ではない(耐性化)ことである。本研究は、患者自身が行える点眼治療の開発を目指すものである。今回、後眼部への薬物輸送ルートが解明され、工業生産に利用可能な新しい点眼剤作製法が見出された。いずれの成果も、HDLという血中に存在する物質の異所(眼表面)での医療応用という点で、学術的にも社会的にも意義が大きい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (28 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] バーゼル大学/薬学研究科(スイス)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Potential of Lipoprotein-Based Nanoparticulate Formulations for the Treatment of Eye Diseases2020

    • Author(s)
      Fukuda, R.; Murakami, T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 4 Pages: 596-607

    • DOI

      10.1248/bpb.b19-00858

    • NAID

      130007825271

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-04-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sustained photodynamic effect of single chirality-enriched single-walled carbon nanotubes2020

    • Author(s)
      Fukuda, R.; Umeyama, T.; Tsujimoto, M.; Ishidate, F.; Tanaka, T.; Kataura, H.; Imahori, H.; Murakami, T.
    • Journal Title

      Carbon

      Volume: 161 Pages: 718-725

    • DOI

      10.1016/j.carbon.2020.02.002

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Control of Lipid Bilayer Phases of Cell-Sized Liposomes by Surface-Engineered Plasmonic Nanoparticles2020

    • Author(s)
      Tomohiro Nobeyama、Kazuki Shigyou、Hirotaka Nakatsuji、Hiroshi Sugiyama、Naoko Komura、Hiromune Ando、Tsutomu Hamada、Tatsuya Murakami
    • Journal Title

      Langmuir

      Volume: 36 Issue: 26 Pages: 7741-7746

    • DOI

      10.1021/acs.langmuir.0c00049

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elucidation of the Mechanisms for the Underlying Depolarization and Reversibility by Photoactive Molecule.2020

    • Author(s)
      Numata Tomohiro、Fukuda Ryosuke、Hirano Mitsuru、Yamaguchi Kazuma、Sato-Numata Kaori、Imahori Hiroshi、Murakami Tatsuya
    • Journal Title

      Cellular Physiology and Biochemistry

      Volume: 54 Issue: 5 Pages: 899-916

    • DOI

      10.33594/000000277

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Membrane fusogenic high-density lipoprotein nanoparticles2020

    • Author(s)
      Kim, H.; Nobeyama, T.; Honda, S.; Yasuda, K.; Morone, N.; and Murakami, T.
    • Journal Title

      Biochem. Biophys. Acta - Biomembrane 2019, 1861, 183008.

      Volume: 1861 Issue: 10 Pages: 183008-183008

    • DOI

      10.1016/j.bbamem.2019.06.007

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Urea-assisted reconstitution of discoidal high-density lipoprotein2020

    • Author(s)
      Fukuda, R.; Saito, M.; Shibukawa, S.; Sumino, A.; Nakano, M.; Murakami, T.
    • Journal Title

      Biochemistry

      Volume: 59 Issue: 15 Pages: 1455-1464

    • DOI

      10.1021/acs.biochem.0c00075

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of the Peripheral Substituents, Central Metal, and Solvent on the Photochemical and Photophysical Properties of 5,15-Diazaporphyrins2019

    • Author(s)
      Satoshi Omomo, Ryosuke Fukuda, Tomoaki Miura, Tatsuya Murakami, Tadaaki Ikoma, and Yoshihiro Matano
    • Journal Title

      ChemPlusChem

      Volume: 84 Issue: 6 Pages: 1-7

    • DOI

      10.1002/cplu.201900087

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Colloidal stability of lipid/protein-coated nanomaterials in salt and sucrose solutions2018

    • Author(s)
      Nobeyama, T.; Mori, M.; Shigyou, K.; Takata, K.; Pandian, G.N.; Sugiyama, H.; Murakami, T.
    • Journal Title

      ChemistrySelect

      Volume: 3 Issue: 28 Pages: 8325-8331

    • DOI

      10.1002/slct.201801180

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 治療用ナノ粒子としてのリポタンパク質変異体2020

    • Author(s)
      河上 亮、福田 亮介、河西 文武、村上 達也
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] リン脂質ナノキャリアの血液循環特性の向上:ゼブラフィッシュスクリーニングモデルを用いた解析2020

    • Author(s)
      島 瑠美奈、福田 亮介、Jeorg Huwyler、村上 達也
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Urea-Assisted Reconstitution of Discoidal High-Density Lipoprotein2020

    • Author(s)
      Ryosuke Fukuda, Mio Saito, Shiori Shibukawa, Ayumi Sumino, Minoru Nakano, Tatsuya Murakami
    • Organizer
      Controlled Release Society 2020 Virtual Annual Meeting
    • Related Report
      2020 Annual Research Report
  • [Presentation] ディスク状脂質ドラッグキャリアの作製・保存法の開発2019

    • Author(s)
      福田 亮介、齊藤 実央、島 瑠美奈、角野 歩、村上 達也
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ディスク状脂質ドラッグキャリアの1ステップ作製法の確立とその形成メカニズム2019

    • Author(s)
      齊藤 実央、福田 亮介、角野 歩、村上 達也
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Deformation and formation of Lo phase domains on cell-sized liposome with membrane-adhesive plasmonic nanoparticles2019

    • Author(s)
      Nobeyama, T.; Shigyo, K.; Nakatsuji, H.; Sugiyama, H.; Hamada, T.; Murakami, T.
    • Organizer
      Materials Research Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 植物細胞とリポタンパク質ドラッグキャリアの相互作用に関する基礎的研究2019

    • Author(s)
      谷 美沙季、延山 知弘、福田 亮介、加藤 康夫、野村 泰治、村上 達也
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脂質/タンパク質ドラッグキャリアの1ステップ作製2018

    • Author(s)
      齊藤 実央、福田 亮介、角野 歩、村上 達也
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 細胞内ドラッグデリバリーシステムを基盤とする光細胞工学2018

    • Author(s)
      村上 達也
    • Organizer
      第70回日本生物工学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ナノリポタンパク質製剤の簡便作製法の確立2018

    • Author(s)
      福田 亮介、齊藤 実央、角野 歩、村上 達也
    • Organizer
      2018年度高分子学会北陸支部研究発表会
    • Related Report
      2018 Research-status Report
  • [Presentation] Lyophilization of Nano-Lipo Eye Drops and Its Effects on the Physicochemical Properties2018

    • Author(s)
      福田 亮介、島 瑠美奈、角野 歩、村上 達也
    • Organizer
      The 5th Toyama-Basel Joint Symposium on Pharmaceutical Research and Development
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] High-Density Lipoprotein Mutant Eye Drops for the Treatment of Age-Related Macular Degeneration2018

    • Author(s)
      村上 達也
    • Organizer
      The 5th Toyama-Basel Joint Symposium on Pharmaceutical Research and Development
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Manipulation ofr Model Lipid Rafts on Cell-Sizd Liposomes by Using Plasma Membrane-Adhesive Gold Nanorods2018

    • Author(s)
      延山 知弘、執行 航希、中辻 博貴、杉山 弘、濱田 勉、村上 達也
    • Organizer
      The 5th Toyama-Basel Joint Symposium on Pharmaceutical Research and Development
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] One Step Reconstitution of Lipid/Protein-Drug Carrier2018

    • Author(s)
      齊藤 実央、福田 亮介、角野 歩、村上 達也
    • Organizer
      The 5th Toyama-Basel Joint Symposium on Pharmaceutical Research and Development
    • Related Report
      2018 Research-status Report
  • [Remarks] 村上達也研究室

    • URL

      https://www.pu-toyama.ac.jp/BR/murakami/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      https://www.pu-toyama.ac.jp/BR/murakami/

    • Related Report
      2019 Research-status Report
  • [Remarks] 富山県立大学 村上研究室HP

    • URL

      https://www.pu-toyama.ac.jp/BR/murakami/index.html

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 薬物デリバリーキャリアおよびこれを用いる医薬品組成物2020

    • Inventor(s)
      村上達也、サウェンラット・カシラワット、福田亮介、他4名
    • Industrial Property Rights Holder
      村上達也、サウェンラット・カシラワット、福田亮介、他4名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-036022
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 薬物デリバリーキャリアおよびこれを用いる医薬組成物2020

    • Inventor(s)
      村上達也,Sawangrat Kasirawat,他5名
    • Industrial Property Rights Holder
      村上達也,Sawangrat Kasirawat,他5名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-036022
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report

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Published: 2018-07-25   Modified: 2022-01-27  

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