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

• Project/Area Number: 21390010
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Nagasaki 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: ¥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.

Research Products

• [Journal Article] Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Nanoparticles electrostatically coated with folic acid for effective gene therapy (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Secure and effective gene vector of polyamidoamine dendrimer pharraac eutically modified with anionic polymer (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration (2011)
  • 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
  • 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(3) Pages: 351-361
  • 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(3) Pages: 404-410
  • NAID: 120006984597
  • 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
  • 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
  • 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 Volume: 30(26) Pages: 4427-4434
  • NAID: 120006984133
  • 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 Volume: 19(2) Pages: 141-147
  • NAID: 120006984575
  • 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 Volume: 136(3) Pages: 213-219
  • NAID: 120006984134
  • 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 Volume: 30(14) Pages: 2846-2853
  • NAID: 120006982935
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Ternary complexes of pDNA with cationic polymer and anionic polymer for secure gene delivery systems (2010)
  • 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
• [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
• [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
• [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
• [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
• [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
• [Presentation] COMPLEX OF PLASMID DNA WITH N-LAUROYLSARCOSINE LIPOSOMES THROUGH CALCIUM BRIDGIHG FOR EFFECTIVE AND SECURE GENE DELIVERY (2009)
  • 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
• [Presentation] INFLUENCE OF DISEASE STAGE ON POLYPLEX AND LIPOPLEX MEDIATED GENE DELIVERY IN MURINE HEPATITIS (2009)
  • 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
• [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
• [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
• [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
• [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
• [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
• [Remarks]
  • URL: http://www.mdp.nagasaki-u.ac.jp/research/achievement.html
• [Remarks]
  • URL: http://www.mdp.nagasaki-u.ac.jp/research/achievement.html
• [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
• [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