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The development of self-assembly nano-devices based on electrostatic interaction and the application to selective drug delivery

Research Project

Project/Area Number 21390010
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionNagasaki University

Principal Investigator

SASAKI Hitoshi  長崎大学, 病院, 教授 (00170689)

Co-Investigator(Kenkyū-buntansha) TO Hideto  富山大学, 大学院・医学薬学研究部(薬学), 教授 (90346809)
KAWAKAMI Shigeru  京都大学, 薬学研究科, 講師 (20322307)
KUROSAKI Tomoaki  長崎大学, 病院・薬剤部, COE研究員 (00582016)
KITAHARA Takashi  長崎大学, 長崎大学病院, 准教授 (30380934)
KODAMA Yukinobu  長崎大学, 大学院・医歯薬学総合研究科, 助教 (50448510)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Keywordsドラッグデリバリー / 遺伝子 / 癌 / ナノ材料 / 遺伝子デリバリー / 葉酸 / グリチルリチン / Drug delivery system / 生体適合型ベクター / 生体分解型ベクター / 自己組織化 / 遺伝子導入技術 / 静電的相互作用 / 低分子リガンド / カチオン性遺伝子ベクター / ナノ微粒子 / 遺伝子導入 / アニオン性高分子 / γ-polyglutamic acid / chondroitin sulfate
Research Abstract

In this study, we developed the self-assembly nano-devices based on electrostatic interaction. We could prepare the stable nano-devices by changing the blend ratio of gene, cationic compounds and anionic compounds and the preparation procedures. The nano-devices containingγ-polyglutamic acid, N-lauroylsarcosine, or glycyrrhizin achieved high intracellular uptake without showing cytotoxicity and blood toxicity. After intravenous administration of these nano-devices in mice, selective high gene expression was observed in the spleen, lung, or liver by the difference of each component. Furthermore, we could mass-produce and freeze-dry nano-devices. In conclusion, we successfully developed the secure and effective nano-devices and revealed the preparation technic responding to therapeutic purpose.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (42 results)

All 2011 2010 2009 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (21 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration2011

    • Author(s)
      Cherif MS, Shuaibu MN, Kurosaki T, Helegbe GK, Kikuchi M, Yanagi T, Tsuboi T, Sasaki H, Hirayama K.
    • Journal Title

      Vaccine

      Volume: 29(48) Pages: 9038-9050

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer2011

    • Author(s)
      Kurosaki T, Yamashita Y, Aki K, Harasawa H, Nakagawa H, Kodama Y, Higuchi N, Nakamura T, Kitahara T, Sasaki H
    • Journal Title

      J Pharm Sci

      Volume: 100(11) Pages: 4855-4863

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nanoparticles electrostatically coated with folic acid for effective gene therapy2011

    • Author(s)
      Kurosaki T, Morishita T, Kodama Y, Sato K, Nakagawa H, Higuchi N, Nakamura T, Hamamoto T, Sasaki H, Kitahara T
    • Journal Title

      Mol Pharm

      Volume: 8(3) Pages: 913-919

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Secure and effective gene vector of polyamidoamine dendrimer pharraac eutically modified with anionic polymer2011

    • Author(s)
      Kurosaki T, Yamashita Y, Aki K, Harasawa H, Nakagawa H, Kodama Y, Higuchi N, Nakamura T, Kitahara T, Sasaki H
    • Journal Title

      J Pharm Sci

      Volume: 100 Issue: 11 Pages: 4855-4863

    • DOI

      10.1002/jps.22701

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration2011

    • Author(s)
      Cherif MS, Shuaibu MN, Kurosaki T, Helegbe GK, Kikuchi M, Yanagi T, Tsuboi T, Sasaki H, Hirayama K
    • Journal Title

      Vaccine

      Volume: 29 Pages: 9038-9050

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chondroitin sulfate capsule system for efficient and secure gene delivery2010

    • Author(s)
      Kurosaki T, Kitahara T, Fumoto S, Nishida K, Yamamoto K, Nakagawa H, Kodama Y, Higuchi N, Nakamura T, Sasaki H
    • Journal Title

      J Pharm Pharm Sci

      Volume: 13(3) Pages: 351-361

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gamma-polyglutamic acid-coated vectors for effective and safe gene therapy2010

    • Author(s)
      Kurosaki T, Kitahara T, Kawakami S, Higuchi Y, Yamaguchi A, Nakagawa H, Kodama Y, Hamamoto T, Hashida M, Sasaki H
    • Journal Title

      J Control Release

      Volume: 142(3) Pages: 404-410

    • NAID

      120006984597

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gamma-polyglutamic acid-coated vectors for effective and safe gene therapy.2010

    • Author(s)
      Kurosaki T, Kitahara T, Kawakami S, Higuchi Y, Yamaguchi A, Nakagawa H, Kodama Y, Hamamoto T, Hashida M, Sasaki H.
    • Journal Title

      J Control Release.

      Volume: 142 Pages: 404-410

    • NAID

      120006984597

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chondroitin sulfate capsule system for efficient and secure gene delivery.2010

    • Author(s)
      Kurosaki T, Kitahara T, Fumoto S, Nishida K, Yamamoto K, Nakagawa H, Kodama Y, Higuchi N, Nakamura T, Sasaki H.
    • Journal Title

      J Pharm Pharm Sci

      Volume: 13 Pages: 351-361

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The development of a gene vector electrostatically assembled with a polysaccharide capsule2009

    • Author(s)
      Kurosaki T, Kitahara T, Kawakami S, Nishida K, Nakamura J, Teshima M, Nakagawa H, Kodama Y, To H, Sasaki H
    • Journal Title

      Biomaterials

      Volume: 30(26) Pages: 4427-4434

    • NAID

      120006984133

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cationic liposomes-mediated plasmid DNA delivery in murine hepatitis induced by carbon tetrachloride2009

    • Author(s)
      Yoshioka T, Yoshida S, Kurosaki T, Teshima M, Nishida K, Nakamura J, Nakashima M, To H, Kitahara T, Sasaki H
    • Journal Title

      J Liposome Res

      Volume: 19(2) Pages: 141-147

    • NAID

      120006984575

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pulmonary gene delivery of hybrid vector, lipopolyplex containing N-lauroylsarcosine, via the systemic route2009

    • Author(s)
      Kurosaki T, Kishikawa R, Matsumoto M, Kodama Y, Hamamoto T, To H, Niidome T, Takayama K, Kitahara T, Sasaki H
    • Journal Title

      J Control Release

      Volume: 136(3) Pages: 213-219

    • NAID

      120006984134

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ternary complexes of pDNA, polyethylenimine, and gamma-polyglutamic acid for gene delivery systems2009

    • Author(s)
      Kurosaki T, Kitahara T, Fumoto S, Nishida K, Nakamura J, Niidome T, Kodama Y, Nakagawa H, To H, Sasaki H
    • Journal Title

      Biomaterials

      Volume: 30(14) Pages: 2846-2853

    • NAID

      120006982935

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ternary complexes of pDNA, polyethylenimine, and gamma-polyglutamic acid for gene delivery systems.2009

    • Author(s)
      Kurosaki, T., Kitahara, T., Fumoto, S., Nishida, K., Nakamura, J., Niidome, T., Kodama, Y., Nakagawa, H., To, H., Sasaki, H.
    • Journal Title

      Biomaterials 30

      Pages: 2846-2853

    • NAID

      120006982935

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pulmonary gene delivery of hybrid vector, lipopolyplex containing N-lauroylsarcosine, via the systemic route.2009

    • Author(s)
      Kurosaki, T., Kishikawa, R., Matsumoto, M., Kodama, Y., Hamamoto, T., To, H., Niidome, T., Takayama, K., Kitahara, T., Sasaki, H.
    • Journal Title

      J.Control. Release 136

      Pages: 213-219

    • NAID

      120006984134

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The development of a gene vector electrostatically assembled with a polysaccharide capsule.2009

    • Author(s)
      Kurosaki, T, Kitahara, T., Kawakami, S., Nishida, K., Nakamura, J., Teshima, M., Nakagawa, H., Kodama, Y., To, H., Sasaki, H.
    • Journal Title

      Biomaterials 30

      Pages: 4427-4434

    • NAID

      120006984133

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cationic liposomes-mediated plasmid DNA delivery in murine hepatitis induced by carbon tetrachloride.2009

    • Author(s)
      Yoshioka, T, Yoshida, S., Kurosaki, T., Teshima, M., Nishida, K., Nakamura, J., Nakashima, M., To, H., Kitahara, T., Sasaki, H.
    • Journal Title

      J.Liposome Res. 23

      Pages: 1-7

    • NAID

      120006984575

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] グリチルリチン被膜型肝指向性遺伝子ベクターの開発2011

    • Author(s)
      川鍋早紀、黒崎友亮、兒玉幸修、北原隆志、佐々木均
    • Organizer
      第28回日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Year and Date
      2011-12-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 三重複合体による新規遺伝子ベクターの開発:コンドロイチン硫酸被膜型デンドリプレックス2011

    • Author(s)
      今村政信、黒崎友亮、兒玉幸修、北原隆志、佐々木均
    • Organizer
      第27回日本DDS学会
    • Place of Presentation
      東京
    • Year and Date
      2011-06-09
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 三重構造を有した生体分解型遺伝子ベクターの構築2011

    • Author(s)
      黒崎友亮、川上茂、橋田充、佐々木均
    • Organizer
      第27回日本DDS学会
    • Place of Presentation
      東京
    • Year and Date
      2011-06-09
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 静電的相互作用を利用した葉酸修飾型遺伝子ベクターの開発2011

    • Author(s)
      黒崎友亮、川上茂、橋田充、佐々木均
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-29
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Dendrimerを用いた三次元型遺伝子ベクターの開発2010

    • Author(s)
      山下祐未、黒崎友亮、森下圭美、兒玉幸修、北原隆志、佐々木均
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎
    • Year and Date
      2010-12-11
    • Related Report
      2011 Final Research Report
  • [Presentation] 自己組織化により形成される葉酸修飾型遺伝子ベクターの開発2010

    • Author(s)
      森下圭美、黒崎友亮、北原隆志、中村忠博、籐秀人、佐々木均
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎
    • Year and Date
      2010-12-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] Dendrimerを用いた三元型遺伝子ベクターの開発2010

    • Author(s)
      山下祐未、黒崎友亮、森下圭美、兒玉幸修、北原隆志、佐々木均
    • Organizer
      第27回日本薬学会九州支部大会
    • Place of Presentation
      長崎
    • Year and Date
      2010-12-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pulmonary gene delivery of hybrid vector, lipopolyplex containing N-lauroylsarcosine, via systemic route.2010

    • Author(s)
      H.Sasaki, T.Kurosaki, H.To, T.Kitahara
    • Organizer
      FIP Pharmaceutical Sciences 2010 world congress
    • Place of Presentation
      New Orleans
    • Year and Date
      2010-11-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Ternary complexes of pDNA with cationic polymer and anionic polymer for secure gene delivery systems2010

    • Author(s)
      T.Kurosaki, T.Kitahara, T.Nakamura, H.Sasaki
    • Organizer
      FIP Pharmaceutical Sciences 2010 world congress
    • Place of Presentation
      New Orleans
    • Year and Date
      2010-11-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 静電的相互作用を基盤とした生体適合型遺伝子ベクターの開発とその応用2010

    • Author(s)
      黒崎友亮
    • Organizer
      日本薬剤学会第35回製剤セミナー
    • Place of Presentation
      静岡
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] γ-Polyglutamic acid被膜型遺伝子ベクターの開発2010

    • Author(s)
      黒崎友亮、北原隆志、兒玉幸修、藤秀人、濱本知之、佐々木均
    • Organizer
      第26回日本DDS学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-06-17
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 脾臓標的化遺伝子ベクターの開発とDNAワクチンベクターへの応用2010

    • Author(s)
      黒崎友亮、北原隆志、兒玉幸修、西田孝洋、麓伸太郎、佐々木均
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      徳島
    • Year and Date
      2010-05-13
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 新規遺伝子ベクターの開発 : カルシウムイオンを介したプラスミドDNA-アニオン性リポソーム複合体2009

    • Author(s)
      中井將人、黒崎友亮、児玉幸修、藤秀人、浜本知之、北原隆志、佐々木均
    • Organizer
      第24回 長崎DDS研究会
    • Place of Presentation
      長崎
    • Year and Date
      2009-12-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] 新規遺伝子ベクターの開発 : カルシウムイオンを介したプラスミドDNA-アニオン性リポソーム複合体2009

    • Author(s)
      中井將人、黒崎友亮、児玉幸修、藤秀人、浜本知之、北原隆志、佐々木均
    • Organizer
      第26回 日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] COMPLEX OF PLASMID DNA WITH N-LAUROYLSARCOSINE LIPOSOMES THROUGH CALCIUM BRIDGIHG FOR EFFECTIVE AND SECURE GENE DELIVERY2009

    • Author(s)
      Masato Nakai, Tomoaki Kurosaki, Yukinobu Kodama, Takashi Kitahara, Hitoshi Sasaki
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2009
    • Place of Presentation
      福岡
    • Year and Date
      2009-10-17
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] INFLUENCE OF DISEASE STAGE ON POLYPLEX AND LIPOPLEX MEDIATED GENE DELIVERY IN MURINE HEPATITIS2009

    • Author(s)
      Hitoshi Sasaki, Tomoaki Kurosaki, Hideto To, Tomoyuki Hamamoto, Takashi Kitahara
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2009
    • Place of Presentation
      福岡
    • Year and Date
      2009-10-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] PULMONARY GENE DELIVERY OF HYBRID VECTOR, LIPOPOLYPLEX CONTAINING N-LAUROYLSARCOSINE, VIASYSTEMIC ROUTE.2009

    • Author(s)
      Tomoaki Kurosaki, Kozo Takayama, Takashi Kitahara, Tomoyuki Hamamoto, Hitoshi Sasaki
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2009
    • Place of Presentation
      福岡
    • Year and Date
      2009-10-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 静電的相互作用を基盤とした多糖被膜型遺伝子ベクターの開発と解析2009

    • Author(s)
      黒崎友亮、濱本知之、北原隆志、藤秀人、佐々木均
    • Organizer
      遺伝子デリバリー研究会 第9回シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肺指向性を持つ全身投与型遺伝子ベクターの開発と解析2009

    • Author(s)
      黒崎友亮、高山幸三、北原隆志、麓伸太郎、西田孝洋、濱本知之、佐々木均
    • Organizer
      第25回日本DDS学会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-03
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] γ-Polyglutamic acid被膜型遺伝子ベクターの開発とメカニズムの解明2009

    • Author(s)
      佐々木均、黒崎友亮、濱本知之、麓伸太郎、西田孝洋、北原隆志
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡
    • Year and Date
      2009-05-23
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 負電荷高分子を用いた被膜型遺伝子導入ベクターの開発2009

    • Author(s)
      黒崎友亮、北原隆志、麓伸太郎、西田孝洋、中村純三、藤秀人、佐々木均
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡
    • Year and Date
      2009-05-21
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.mdp.nagasaki-u.ac.jp/research/achievement.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.mdp.nagasaki-u.ac.jp/research/achievement.html

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規ナノボールの創製2010

    • Inventor(s)
      佐々木均、黒崎友亮、北原隆志、他
    • Industrial Property Rights Holder
      国立大学法人長崎大学
    • Industrial Property Number
      2010-043186
    • Filing Date
      2010-02-26
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 薬物送達複合体2010

    • Inventor(s)
      佐々木均, 黒崎友亮, 北原隆志, 藤秀人, 由井克之, 平山謙二, 森田公一
    • Industrial Property Rights Holder
      長崎大学
    • Industrial Property Number
      2010-043186
    • Filing Date
      2010-02-26
    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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