Development of transscleral multi-drug delivery device for retinal disease treatment

• Project/Area Number: 15H03015
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Tohoku University
• Principal Investigator: Nagai Nobuhiro 東北大学, 医学系研究科, 助教 (30400039)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 薬物送達 / 生体材料 / 眼科学 / 網膜 / ドラッグデリバリーシステム / 臨床応用 / 経強膜投与 / 薬学 / バイオテクノロジー / 網膜疾患 / DDS

Outline of Final Research Achievements

Purpose is the evaluation of a transscleral multi-drug delivery device for clinical practice. We developed a flexible device that can fit on the curvature of the eyeball by using a silicon material and stainless wire. Pharmacokinetics in the eye was evaluated for 1 year using rabbits and monkeys. Safety in the retinal function 1 year after device implantation was confirmed. Pharmacological effects in transgenic retinal degeneration model rabbits was confirmed. Scar formation around the device did not affect the retinal function. Enhanced drug delivery by simultaneous cyclosporine A release was indicated. Devices for clinical use was stable for 24 months and safe biologically.

Research Products

• [Journal Article] Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes (2018)
  • Author(s): Nagai Nobuhiro、Yamada Shinji、Kawasaki Junichi、Koyanagi Eri、Saijo Saaya、Kaji Hirokazu、Nishizawa Matsuhiko、Nakazawa Toru、Abe Toshiaki
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 59 Issue: 2 Pages: 644-644
  • DOI: 10.1167/iovs.17-22429
  • Peer Reviewed
• [Journal Article] In situ formation of injectable chitosan-gelatin hydrogels through double crosslinking for sustained intraocular drug delivery (2018)
  • Author(s): Song Yuanhui、Nagai Nobuhiro、Saijo Saaya、Kaji Hirokazu、Nishizawa Matsuhiko、Abe Toshiaki
  • Journal Title: Materials Science & Engineering C Volume: 88 Pages: 1-12
  • DOI: 10.1016/j.msec.2018.02.022
  • Peer Reviewed
• [Journal Article] Controlled basic fibroblast growth factor release device made of poly(ethyleneglycol) dimethacrylates for creating a subcutaneous neovascular bed for cell transplantation (2017)
  • Author(s): Yamada Shinji、Nagai Nobuhiro、Saijo Saaya、Kaji Hirokazu、Nishizawa Matsuhiko、Imura Kozue、Goto Masafumi、Abe Toshiaki
  • Journal Title: Journal of Biomedical Materials Research Part B: Applied Biomaterials Volume: 105 Issue: 11 Pages: 3017-3024
  • DOI: 10.1002/jbm.a.36153
  • Peer Reviewed
• [Journal Article] Drug delivery devices for retinal diseases (2017)
  • Author(s): Kaji Hirokazu、Nagai Nobuhiro、Nishizawa Matsuhiko、Abe Toshiaki
  • Journal Title: Advanced Drug Delivery Reviews Volume: - Pages: 148-157
  • DOI: 10.1016/j.addr.2017.07.002
  • Peer Reviewed
• [Journal Article] Microfluidic co-cultures of retinal pigment epithelial cells and vascular endothelial cells to investigate choroidal angiogenesis (2017)
  • Author(s): Chen Li-Jiun、Ito Shuntaro、Kai Hiroyuki、Nagamine Kuniaki、Nagai Nobuhiro、Nishizawa Matsuhiko、Abe Toshiaki、Kaji Hirokazu
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 3538-3538
  • DOI: 10.1038/s41598-017-03788-5
  • Peer Reviewed / Open Access
• [Journal Article] Physicochemical and biological characterization of sustained isopropyl unoprostone-release device made of poly(ethyleneglycol) dimethacrylates (2017)
  • Author(s): Nagai Nobuhiro、Izumida Yasuko、Yamazaki Yoshimasa、Kaji Hirokazu、Kawasaki Junichi、Nishizawa Matsuhiko、Abe Toshiaki
  • Journal Title: Journal of Materials Science: Materials in Medicine Volume: 28 Issue: 7 Pages: 1-7
  • DOI: 10.1007/s10856-017-5919-2
  • Peer Reviewed
• [Journal Article] Long-term Protection of Genetically-Ablated Rabbit Retinal Degeneration by Sustained Transscleral Unoprostone Delivery (2017)
  • Author(s): Nobuhiro Nagai, Eri Koyanagi, Yasuko Izumida, Junjun Liu, Aya Katsuyama, Hirokazu Kaji, Matsuhiko Nishizawa, Noriko Osumi, Mineo Kondo, Hiroko Terasaki, Yukihiko Mashima, Toru Nakazawa, Toshiaki Abe
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 57(15) Issue: 15 Pages: 6527-6538
  • DOI: 10.1167/iovs.16-20453
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A self-deploying drug release device using polymeric films (2017)
  • Author(s): Taro Kondo, Zhaleh Kashkouli Nezhad, Jin Suzuki, Nobuhiro Nagai, Matsuhiko Nishizawa, Toshiaki Abe, Hirokazu Kaji
  • Journal Title: Journal of Biomedical Materials Research Part B: Applied Biomaterials Volume: in press Issue: 2 Pages: 780-786
  • DOI: 10.1002/jbm.b.33887
  • Peer Reviewed / Open Access
• [Journal Article] Transscleral Controlled Delivery of Geranylgeranylaceton Using a Polymeric Device Protects Rat Retina Against Light Injury (2016)
  • Author(s): Nagai N, Kaji H, Nishizawa M, Nakazawa T, Abe T
  • Journal Title: Adv Exp Med Biol Volume: 854 Pages: 471-477
  • DOI: 10.1007/978-3-319-17121-0_63
  • ISBN: 9783319171203, 9783319171210
  • Peer Reviewed / Open Access
• [Journal Article] Protective effects of transscleral sustained unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats (2015)
  • Author(s): Nobuhiro Nagai, Satoru Iwata, Kaori Sampei, Hideyuki Onami, Hirokazu Kaji, Matsuhiko Nishizawa, Toru Nakazawa, Yukihiko Mashima, Toshiaki Abe
  • Journal Title: Journal of Biomedical Materials Research Part B: Applied Biomaterials Volume: in press Issue: 8 Pages: 1730-1737
  • DOI: 10.1002/jbm.b.33522
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Application of clotrimazole via a novel controlled release device provides potent retinal protection (2015)
  • Author(s): Zhaleh Kashkouli Nezhad, Nobuhiro Nagai, Kotaro Yamamoto, Hirokazu Kaji, Matsuhiko Nishizawa, Hideyuki Saya, Toru Nakazawa, Toshiaki Abe
  • Journal Title: J Mater Sci Mater Med Volume: 26 Issue: 9 Pages: 5561-5561
  • DOI: 10.1007/s10856-015-5561-9
  • Peer Reviewed / Open Access
• [Presentation] 再注入可能な持続性薬物徐放デバイスおよび再充填用インジェクタブルゲルの開発 (2017)
  • Author(s): 西條早絢、永井展裕、Song Yuanhui、阿部俊明
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2017-03-07
• [Presentation] Biodegradable injectable sheet as transscleral drug delivery system (2017)
  • Author(s): Nobuhiro Nagai, Zhaleh Kashikouli Nezhad, Saaya Saijo, Hirokazu Kaji, Matsuhiko Nishizawa, Toru Nakazawa, Toshiaki Abe
  • Organizer: 2017 ARVO annual meeting
  • Int'l Joint Research
• [Presentation] Non-histone nuclear protein play important roles for photoreceptor function and experimental choroidal neovascularization (2017)
  • Author(s): Toshiaki Abe, Aya Katsuyama, Shinji Yamada, Nobuhiro Nagai, Reiko Daigaku, Kenta Ishida, Yuki Katsukura
  • Organizer: 2017 ARVO annual meeting
  • Int'l Joint Research
• [Presentation] ウノプロストン徐放デバイスのサル強膜上12箇月間留置における眼内動態と眼毒性評価 (2017)
  • Author(s): 永井展裕、山田慎二、西條早絢、川崎淳一、梶弘和、中澤徹、西澤松彦、阿部俊明
  • Organizer: 第33回日本DDS学会学術集会
• [Presentation] 再注入可能および持続的なシクロスポリンA徐放カプセルの開発 (2017)
  • Author(s): 西條早絢、永井展裕、梶弘和、阿部俊明
  • Organizer: 第33回日本DDS学会学術集会
• [Presentation] 後眼部局所持続投与を指向した薬物徐放デバイスの開発 (2016)
  • Author(s): 永井展裕、梶弘和、泉田泰子、山田慎二、中澤徹、西澤松彦、眞島行彦、阿部俊明
  • Organizer: 第32回日本DDS学会学術集会
  • Place of Presentation: グランシップ静岡（静岡市）
  • Year and Date: 2016-06-30
• [Presentation] Protective Effects of Sustained Unoprostone Release Device in Rhodopsin Pro347Leu Transgenic Rabbits (2016)
  • Author(s): Nobuhiro Nagai, Yasuko Izumida, Hirokazu Kaji, Matsuhiko Nishizawa, Aya Katsuyama, Shinji Yamada, Toru Nakazawa, Mineo Kondo, Hiroko Terasaki, Yukihiko Mashima, Toshiaki Abe
  • Organizer: 2016 ARVO annual meeting
  • Place of Presentation: Seattle, Washington, USA
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] A non-histone nuclear protein enhances VEGF expression and choroidal neovascularization (2016)
  • Author(s): Toshiaki Abe, Aya Katsuyama, Shinji Yamada, Yuki Katsukura, Zhaleh Kashkouli Nezhad, Nobuhiro Nagai
  • Organizer: 2016 ARVO annual meeting
  • Place of Presentation: Seattle, Washington, USA
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] 網膜色素変性モデルウサギに対するウノプロストン徐放デバイスの網膜保護効果 (2016)
  • Author(s): 永井展裕、泉田泰子、梶弘和、勝山綾、中澤徹、近藤峰生、寺崎浩子、西澤松彦、山田慎二、眞島行彦、阿部俊明
  • Organizer: 第120回日本眼科学会総会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2016-04-07
• [Presentation] 網膜色素変性症治療を目指した薬剤徐放デバイスの開発 (2016)
  • Author(s): 永井展裕、泉田泰子、梶弘和、勝山綾、西澤松彦、山田慎二、眞島行彦、阿部俊明
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] Polymeric device based on UV-cured poly(ethyleneglycol) dimethacrylates for controlled intraocular drug delivery (2015)
  • Author(s): Nobuhiro Nagai, Yasuko Izumida, Remi Motoyama, Eri Koyanagi, Aya Katsuyama, Shinji Yamada, Hirokazu Kaji, Matsuhiko Nishizawa, Toshiaki Abe
  • Organizer: Pacifichem2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] 持続性抗がん剤マルチ徐放デバイスの開発 (2015)
  • Author(s): 永井展裕、勝山綾、泉田泰子、小柳恵理、山田慎二、梶弘和、阿部俊明
  • Organizer: 第37回バイオマテリアル学会大会
  • Place of Presentation: 京都テルサ（京都府京都市）
  • Year and Date: 2015-11-09
• [Presentation] ミクロ細孔を有するタンパク質徐放デバイスに関する検討 (2015)
  • Author(s): 山田慎二、永井展裕、勝山綾、泉田泰子、小柳恵理、梶弘和、阿部俊明
  • Organizer: 第37回バイオマテリアル学会大会
  • Place of Presentation: 京都テルサ（京都府京都市）
  • Year and Date: 2015-11-09
• [Presentation] Controlled drug release device fabricated with PDMS mold-based UV curing of polyethyleneglycol dimethacrylates (2015)
  • Author(s): Shinji Yamada, Nobuhiro Nagai, Hirokazu Kaji, Aya Katsuyama, Matsuhiko Nishizawa, Toshiaki Abe
  • Organizer: BMES 2015 annual meeting
  • Place of Presentation: Tampa, Florida, USA
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] Sustained release system of ranibizumab for transscleral administration (2015)
  • Author(s): Toshiaki Abe, Shinji Yamada, Hirokazu Kaji, Aya Katsuyama, Matsuhiko Nishizawa, Nobuhiro Nagai
  • Organizer: BMES 2015 annual meeting
  • Place of Presentation: Tampa, Florida, USA
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] Injectable Ultrathin Polymeric Films for Subretinal Cell Delivery (2015)
  • Author(s): Hirokazu Kaji, Taro Kondo, Nobuhiro Nagai, Toshiaki Abe
  • Organizer: BMES 2015 annual meeting
  • Place of Presentation: Tampa, Florida, USA
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] ウノプロストン経強膜持続投与デバイスの開発 (2015)
  • Author(s): 永井展裕、泉田泰子、梶弘和、勝山綾、西澤松彦、山田慎二、眞島行彦、阿部俊明
  • Organizer: 第35回日本眼薬理学会
  • Place of Presentation: ソラシティカンファレンスセンター（東京都千代田区）
  • Year and Date: 2015-09-05
• [Presentation] Development of Injectable Nanosheets as Promising Drug Delivery Systems for Retinal Diseases (2015)
  • Author(s): Zhaleh Kashkouli Nezhad、梶弘和、近藤太郎、永井展裕、西澤松彦、阿部俊明
  • Organizer: 第35回日本眼薬理学会
  • Place of Presentation: ソラシティカンファレンスセンター（東京都千代田区）
  • Year and Date: 2015-09-05
• [Presentation] 低侵襲で持続的な後眼部DDSの開発 (2015)
  • Author(s): 永井展裕
  • Organizer: 第1回東北ドラッグデリバリーシステム研究会
  • Place of Presentation: 東北大学学際科学フロンティア研究所１階セミナー室（宮城県仙台市）
  • Year and Date: 2015-08-10
  • Invited
• [Presentation] Polymeric Device for Transscleral Drug Delivery to the Posterior Segment of the eye (2015)
  • Author(s): Nobuhiro Nagai, Toshiaki Abe
  • Organizer: ソウル大学・香港大学・東北大学Joint Conference in Sendai 2015
  • Place of Presentation: 仙台ウェスティンホテル（宮城県仙台市）
  • Year and Date: 2015-08-05
  • Int'l Joint Research / Invited
• [Presentation] ウノプロストン徐放デバイスによる網膜内局所持続投与の評価 (2015)
  • Author(s): 永井展裕、泉田泰子、梶弘和、本山玲美、西澤松彦、中澤徹、眞島行彦、阿部俊明
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル新宿（東京都新宿区）
  • Year and Date: 2015-07-02
• [Presentation] Injectable degradable/non-bidegradable micropatterned nanosheets for the treatment of eye disease (2015)
  • Author(s): Zhaleh Kashkouli Nezhad、梶弘和、近藤太郎、永井展裕、西澤松彦、阿部俊明
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル新宿（東京都新宿区）
  • Year and Date: 2015-07-02
• [Presentation] 高分子薄膜を用いた薬剤徐放デバイスの開発 (2015)
  • Author(s): 近藤太郎、Zhaleh Kashkouli Nezhad、永井展裕、西澤松彦、阿部俊明、梶弘和
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル新宿（東京都新宿区）
  • Year and Date: 2015-07-02
• [Presentation] Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device (2015)
  • Author(s): Nobuhiro Nagai, Yasuko Izumida, Eri Koyanagi, Hirokazu Kaji, Matsuhiko Nishizawa, Takahito Imagawa, Akiko Morikawa, Toru Nakazawa, Yukihiko Mashima, Toshiaki Abe
  • Organizer: 2015 ARVO annual meeting
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2015-05-03
  • Int'l Joint Research
• [Presentation] Transscleral Sustained Ranibizumab Delivery Device Using Polyethyleneglycol Dimethacrylates (2015)
  • Author(s): Toshiaki Abe, Aya Katsuyama, Hideyuki Onami, Toru Nakazawa, Nobuhiro Nagai
  • Organizer: 2015 ARVO annual meeting
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 2015-05-03
  • Int'l Joint Research
• [Presentation] 経強膜持続投与デバイスの眼毒性評価 (2015)
  • Author(s): 永井展裕、泉田泰子、小柳恵理、梶弘和、西澤松彦、中澤徹、眞島行彦、阿部俊明
  • Organizer: 第119回日本眼科学会総会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2015-04-16
• [Book] DDS先端技術の製剤への応用開発 (2017)
  • Author(s): 阿部俊明、永井展裕
  • Total Pages: 492
  • Publisher: 技術情報協会
  • ISBN: 4861046637
• [Patent(Industrial Property Rights)] 薬物を再注入可能な持続性薬物徐放デバイスおよび再充填用のインジェクタブルゲル (2017)
  • Inventor(s): 阿部俊明、西條早絢、永井展裕
  • Industrial Property Rights Holder: 阿部俊明、西條早絢、永井展裕
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-017163
  • Filing Date: 2017
  • Overseas
• [Patent(Industrial Property Rights)] 薬物を再注入可能な持続性薬物徐放デバイスおよび再充填用のインジェクタブルゲル (2017)
  • Inventor(s): 1. 阿部俊明、西條早絢、永井展裕
  • Industrial Property Rights Holder: 1. 阿部俊明、西條早絢、永井展裕
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-017163
  • Filing Date: 2017-02-28