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Drug delivery control based on assembly mediated by surface modification of phospholipid vesicles

Research Project

Project/Area Number 17300162
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionWaseda University

Principal Investigator

SOU Keitaro  Waseda University, Faculty of Science and Engineering, Associate professor (20318835)

Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥11,320,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥8,100,000 (Direct Cost: ¥8,100,000)
Keywordsnanoparticle / amphiphile / molecular assembly / phospholipid vesicle / surface modification / biodistribution / targeting / drug delivery system / 表面装飾 / 標識指向性
Research Abstract

Nanoparticulate phospholipid vesicles(liposomes) are in wide use as carriers of drugs, proteins, and genes etc. for the therapeutic purposes. However, conventional nanoparticles including vesicles were mostly distributed into liver and spleen after injection. This study provided novel concept to achieve targeting of bone marrow by using phospholipids vesicles as carrier in vivo. Two compounds, an original anionic amphiphile and conventional polyethylene glycol(PEG)-lipid, were key materials to modify the surface of vesicles for significant targeting to bone marrow macrophages in vivo. We demonstrated that more than 60% of intravenous injected vesicles selectively accumulated into bone marrow within 6h after injection in rabbits.
In addition, our observations indicated that the responsible cellar pathway into bone marrow from blood circulation is the endocytosis by bone marrow macrophages. There is no effective drug delivery system which can target bone marrow right now. The efficient delivery of encapsulated scintigraphic and fluorescent imaging agents to bone marrow macrophages suggests that vesicles are promising carriers for the specific targeting of bone marrow macrophages and may be useful for delivering a wide range of therapeutic agents to bone marrow.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (52 results)

All 2008 2007 2006 2005

All Journal Article (21 results) (of which Peer Reviewed: 9 results) Presentation (20 results) Book (7 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 results)

  • [Journal Article] Hemoglobin-vesicles as artificial oxygen carriers: Present situation and future vision2008

    • Author(s)
      H.Sakai, K.Sou, H.Horinouchi, K.Kobayashi, E.Tsuchida
    • Journal Title

      J.Intern.Med. 263

      Pages: 4-15

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Loading of curcumin into macrophages using lipid-based nanoparticles2008

    • Author(s)
      K.Sou, S.Inenaga, S.Takeoka, E.Tsuchida
    • Journal Title

      Int.J.Pharm. 352

      Pages: 287-293

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Electrostatic interactions and complement activation on the surface of phospholipid vesicles containing acidic lipids: Effect of the structure of acidic groups2008

    • Author(s)
      K.Sou, E.Tsuchida
    • Journal Title

      Biochim.Biophys.Acta-Biomembranes 1778

      Pages: 1035-1041

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hemoglobin-vesicles as artificial oxygen carriers : Present situation and future vision2008

    • Author(s)
      H. Sakai, K. Sou, H. Horinouchi, K. Kobayashi, E. Tsuchida
    • Journal Title

      J. Intern. Med. 263

      Pages: 4-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Loading of curcumin into macrophages using lipid-based nanoparticles Int. J. Pharm, 352, 287-293(2008).2008

    • Author(s)
      K. Sou, S. Inenaga, S. Takeoka, E. Tsuchida
    • Journal Title

      Int. J. Pharm 352

      Pages: 287-293

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Electrostatic interactions and complement activation on the surface of phospholipid vesicles containing acidic lipids: Effect of the structure of acidic groups2008

    • Author(s)
      K. Sou, E. Tsuchida
    • Journal Title

      Biochim. Biophys. Acta-Biomembranes 1778

      Pages: 1035-1041

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Phospholipid vesicles containing acidic lipids:Effect of the structure of acidic groups2008

    • Author(s)
      K.Sou, E.Tsuchida
    • Journal Title

      Biochim.Biophys.Acta-Biomembranes 1778

      Pages: 1035-1041

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hemoglobin-vesicles as artificial oxygen carriers:Present situation and futurevision2008

    • Author(s)
      H.Sakai, K.Sou, H.Horinouchi, K.Kobayashi, E.Tsuchida
    • Journal Title

      J.Intern.Med. 263

      Pages: 4-15

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poly(ethylene glycol)-conjugated phospholipids in aqueous micellar solutions: Hydration,static Structure,and interparticle interactions2007

    • Author(s)
      T.Sato, H.Sakai, K.Sou, R.Buchner, E.Tsuchida
    • Journal Title

      J.Phys.Chem.B. 111

      Pages: 1393-1401

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Selective uptake of surface-modified phospholipid vesicles by bone marrow macrophages in vivo2007

    • Author(s)
      K.Sou, B.Goins, S.Takeoka, E.Tsuchida, W.T.Phillips
    • Journal Title

      Biomaterials 28

      Pages: 2655-2666

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Solution to the problems of acellular Hbs by encapsulation,and the intrinsic issues of Hb-vesicles as a molecular assembly2007

    • Author(s)
      H.Sakai, K.Sou, E.Tsuchida
    • Journal Title

      Transfus.Altern.Transfus.Med. 9

      Pages: 226-236

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Poly(ethylene glycol)-conjugated phospholipids in aqueous micellar solutions : Hydration, static Structure, and interparticle interactions2007

    • Author(s)
      T. Sato, H. Sakai, K. Sou, R. Buchner, E. Tsuchida
    • Journal Title

      J.phys. Chem. B. 111

      Pages: 1393-401

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Selective uptake of surface-modified phospholipid vesicles by bone marrow macrophages in vivo2007

    • Author(s)
      K. Sou, B. Goins, S. Takeoka, E. Tsuchida, W. T. Phillips
    • Journal Title

      28

      Pages: 2655-2666

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Solution to the problems of acellular Hbs by encapsulation, and the intrinsic issues of Hb-vesicles as a molecular assembly2007

    • Author(s)
      H. Sakai, K. Sou, E. Tsuchida
    • Journal Title

      Transfus. 9

      Pages: 226-236

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Solution to the Problems of acellular Hbs by encapsulation, and the intrinsic issues of Hb-vesicles as a molecuiar assembly2007

    • Author(s)
      H.Sakai, K.Sou, E.Tsuchida,
    • Journal Title

      Transfus.Altern.Transfus.Med. 9

      Pages: 226-236

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective uptake of surface-modified phospholipid vesicles by bone marrow macrophages2007

    • Author(s)
      K.Sou, B.Goins, S.Takeoka, E.Tsuchida, W.T.Phillips
    • Journal Title

      Biomaterials 28

      Pages: 2655-2666

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hemoglobin-vesicles as a molecular assembly : characteristics of preparation process and performances as artificial oxygen carriers2006

    • Author(s)
      H. Sakai, K. Sou, S. Takeoka, K. Kobayashi, E. Tsuchida
    • Journal Title

      In : Blood Substitutes(Ed. By Robert M. Winslow, Elsevier)

      Pages: 514-522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Safety and efficacy of hemoglobin-vesicles and albumin-hemes2005

    • Author(s)
      K. Kobayashi, H. Horinouchi, M. Watanabe, Y. Izumi, Y. Teramura, A. Nakagawa, Y. Huang, K. Sou, H. Sakai, T. Komatsu, S. Takeoka, E. Tsuchida
    • Journal Title

      In : Artificial Oxygen Carrier, Its Front line : Keio University International Symposia for Life Sciences and Medicine Vol.12

      Pages: 1-12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hemoglobin-vesicles(HbV) as artificial oxygen carriers2005

    • Author(s)
      H. Sakai, K. Sou, S. Takeoka, K. Kobayashi, E. Tsuchida
    • Journal Title

      In : Artificial Oxygen Carrier, Its Front line : Keio University International Symposia for Life Sciences and Medicine(Springer-Verlag) Vol.12

      Pages: 135-168

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Circulation kinetics and organ distribution of Hb-vesicles developed as a red blood cell substitute.2005

    • Author(s)
      Sou K, Klipper R, Goins B, Tsuchida E, Phillips WT.
    • Journal Title

      J.Pharmacol.Exp.Ther. 31

      Pages: 702-709

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Oxygen infusions (hemoglobin-vesicles and albumin-hemes) based on nano-molecular sciences.2005

    • Author(s)
      Tsuchida E, Sakai H, Komatsu T, Takeoka S, H.uang Y, Sou K, et al.
    • Journal Title

      Polymers Adv.Technol. 16

      Pages: 73-83

    • Related Report
      2005 Annual Research Report
  • [Presentation] カルボン酸型脂質で表面修飾した微粒子の薬物輸送体としての評価2007

    • Author(s)
      宗 慶太郎, 稲永 俊介, 武岡 真司, 土田 英俊
    • Organizer
      高分子年次大会
    • Place of Presentation
      京都
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Physicochemical characteristics and biodistribution of vesicles modified with carboxylic acids and poly(ethylene glycol)2007

    • Author(s)
      K.Sou and E.Tsuchida
    • Organizer
      12th IUPAC International Symposium on MacroMolecular Complexes
    • Place of Presentation
      Fukuoka
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Surface characteristics of hemoglobin-vesicles: Electrostatic properties and interaction with blood components"2007

    • Author(s)
      K.Sou, H.Sakai, E.Tsuchida
    • Organizer
      The XIth International Symposium on Blood Substitutes
    • Place of Presentation
      Beijing,China
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Organ specific distribution of surface modified nanoparticles with carboxylic acids and poly(ethylene glycol)2007

    • Author(s)
      K.Sou, B.Goins, W.T.Phillips, E.Tsuchida
    • Organizer
      9th International Symposium on Polymers for Advanced Technologies
    • Place of Presentation
      Shanghai,China
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Hemoglobin-vesicles as a molecular assembly: physicochemical characterization and physiological performances as a transfusion alternative2007

    • Author(s)
      E.Tsuchida, K.Sou, H.Sakai, K.Kobayashi
    • Organizer
      9th International Symposium on Polymers for Advanced Technologies
    • Place of Presentation
      Shanghai,China
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Surface characteristics of hemoglobin-vesicles : Electrostatic properties and interaction with blood components2007

    • Author(s)
      K. Sou, H. Sakai, E. Tsuchida
    • Organizer
      The XIth International Symposium on Blood Substitutes
    • Place of Presentation
      Beijing, China
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Organ specific distribution of surface modified nanoparticles with carboxylic acids and poly(ethylene glycol)2007

    • Author(s)
      K. Sou, B. Goins, W.T. Phillips, E. Tsuchida
    • Organizer
      9th International Symposium on Polymers for Advanced Technologies
    • Place of Presentation
      Shanghai, China
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Hemoglobin-vesicles as a molecular assembly : physicochemical characterization and physiological performances as a transfusion alternative(INVITED LECTURE)2007

    • Author(s)
      E. Tsuchida, K. Sou(speaker), H. Sakai, K. Kobayashi
    • Organizer
      9th International Symposium on Polymers for Advanced Technologies
    • Place of Presentation
      Shanghai, China
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Surface characteristics of hemoglobin-vesicles:Electrostatic properties and interaction with blood components2007

    • Author(s)
      K.Sou, H.Sakai, E.Tsuchida
    • Organizer
      The XIth International Symposium on Blood Substitutes
    • Place of Presentation
      Beijing, China
    • Related Report
      2007 Annual Research Report
  • [Presentation] Organ specific distribution of surface modified nanoparticles with carboxylicacids and poly(ethylene glycol)2007

    • Author(s)
      K.Sou, B.Goins, W.T.Phillips, E.Tsuchida
    • Organizer
      9th International Symposium on Polymers for Advanced Technologies
    • Place of Presentation
      Sharlghai, China
    • Related Report
      2007 Annual Research Report
  • [Presentation] 表面修飾小胞体を利用する骨髄への薬物輸送2006

    • Author(s)
      宗 慶太郎, 土田 英俊
    • Organizer
      高分子討論会
    • Place of Presentation
      富山
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 負電荷脂質を含有する油滴小球への脂溶性薬物担持と物性評価2006

    • Author(s)
      稲永 俊介, 宗 慶太郎, 武岡 真司, 土田 英俊
    • Organizer
      高分子討論会
    • Place of Presentation
      富山
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Selective Uptake of Vesicles by Bone Marrow2006

    • Author(s)
      K.Sou, B.Goins, S.Takeoka, E.Tsuchida, WT Phillips
    • Organizer
      International Liposome Society Annual Meeting
    • Place of Presentation
      London,UK
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Selective Uptake of Vesicles by Bone Marrow2006

    • Author(s)
      K. Sou, B. Goins, S. Takeoka, E. Tsuchida, WT Phillips
    • Organizer
      International Liposome Society Annual Meeting
    • Place of Presentation
      London, UK
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 人工赤血球(ヘモグロビン小胞体)の血中半減期と代謝臓器への分布過程2005

    • Author(s)
      宗 慶太郎, Beth Goins, William T.Phillips, 酒井 宏水, 武岡 真司, 土田 英俊
    • Organizer
      高分子年次大会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ポリエチレングリコール鎖を結合した両親媒性化合物によるリン脂質小胞体の表面修飾とヘモグロビン小胞体の安定化効果2005

    • Author(s)
      宗 慶太郎, 武岡 真司, 土田 英俊
    • Organizer
      日本血液代替物学会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 表面修飾小胞体の体内動態特性2005

    • Author(s)
      宗 慶太郎, Beth Goins, William T.Phillips, 武岡 真司, 土田 英俊
    • Organizer
      高分子討論会
    • Place of Presentation
      山形
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 気液界面光反応を効率化した装置を用いたヘモグロビン小胞体の配位子交換2005

    • Author(s)
      鈴木 大祐, 武岡 真司, 宗 慶太郎, 土田 英俊
    • Organizer
      高分子討論会
    • Place of Presentation
      山形
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Circulation kinetics and organ distribution of hemoglobin-vesicles (HbV)2005

    • Author(s)
      K.Sou, B.Goins, W.T.Phillips, H.Sakai, S.Takeoka, and E.Tsuchida
    • Organizer
      The Xth international Symposium on Blood Substritutes
    • Place of Presentation
      Providence,Rhode Island,USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Circulation kinetics and organ distribution of hemoglobin-vesicles(HbV)2005

    • Author(s)
      K. Sou, B. Goins, W.T. Phillips, H. Sakai, S. Takeoka, E. Tsuchida
    • Organizer
      The Xth international Symposium on Blood Substritutes
    • Place of Presentation
      Providence, Rhode Island, USA.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] "Hemoglobin-vesicles as a molecular assembly:characteristics of preparation process and performances as artificial oxygen carriers", In: Blood Substitutes (Ed.By Robert M.Winslow)2006

    • Author(s)
      H.Sakai, K.Sou, S.Takeoka, K.Kobayashi, E.Tsuchida
    • Total Pages
      9
    • Publisher
      Elsevier
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Blood Substitutes2006

    • Author(s)
      Sakai H, Sou K, Takeoka S, Kobayashi K, Tsuchida E
    • Publisher
      Elsevier
    • Related Report
      2005 Annual Research Report
  • [Book] "Safety and efficacy of hemoglobin-vesicles and albumin-hemes", In:Artificial Oxygen Carrier, Its Front line:Keio University International Symposia for Life Sciences and Medicine Vol.122005

    • Author(s)
      K.Kobayashi, H.Horinouchi, M.Watanabe, Y.Izumi, Y.Teramura, A.Nakagawa, Y.Huang, K.Sou, H.Sakai, T.Komatsu, S.Takeoka, E.Tsuchida
    • Total Pages
      20
    • Publisher
      Springer-Verlag
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] "Hemoglobin-vesicles(HbV) as artificial oxygen carriers", In:Artificial Oxygen Carrier, Its Front line:Keio University International Symposia for Life Science and Medicine Vol.122005

    • Author(s)
      H.Sakai, K.Sou, S.Takeoka, K.Kobayashi, E.Tsuchida
    • Total Pages
      34
    • Publisher
      Springer-Verlag
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] "人工赤血球", In:医療用マテリアルと機能膜 第II編 人工臓器 第5章2005

    • Author(s)
      酒井 宏水, 宗 慶太郎, 武岡 真司, 小林 紘一, 土田 英俊
    • Total Pages
      12
    • Publisher
      シーエムシー出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Artificial Oxygen Carrier : Its Front Line Carrier : Its Front Line2005

    • Author(s)
      Sakai H, Sou K, Takeoka S, Kobayashi K, Tsuchida E.
    • Publisher
      Springer-Verlag
    • Related Report
      2005 Annual Research Report
  • [Book] 医療用マテリアルと機能膜 第5章 人工赤血球2005

    • Author(s)
      酒井宏水, 宗慶太郎, 武岡真司, 小林紘一, 土田英俊
    • Publisher
      (株)シーエムシー出版
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] Bone marrow-directing drug delivery materials and their applications2006

    • Inventor(s)
      宗 慶太郎, 他4名
    • Industrial Property Rights Holder
      早稲田大学 テキサス大学
    • Filing Date
      2006-07-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Overseas
  • [Patent(Industrial Property Rights)] Bone marrow-directing drug delivery materials and applications2006

    • Inventor(s)
      宗慶太郎 他4名
    • Industrial Property Rights Holder
      早稲田大学, テキサス大学
    • Filing Date
      2006-06-05
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 骨髄指向性輸送体およびその用途2005

    • Inventor(s)
      宗 慶太郎, 他4名
    • Industrial Property Rights Holder
      早稲田大学 テキサス大学
    • Industrial Property Number
      2005-165763
    • Filing Date
      2005-06-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 骨髄指向性輸送体およびその用途2005

    • Inventor(s)
      宗 慶太郎外4名
    • Industrial Property Rights Holder
      早稲田大学・テキサス大学
    • Filing Date
      2005-06-06
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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