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Creation of High Performance Biocompatible Surface by Surface modification agent which Constructs High Density Tethered Chains

Research Project

Project/Area Number 10558139
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biomedical engineering/Biological material science
Research InstitutionSCIENCE UNIVERSITY OF TOKYO

Principal Investigator

NAGASAKI Yukio  Science University of Tokyo, Materials Science, Associate Professor, 基礎工学部, 助教授 (90198309)

Co-Investigator(Kenkyū-buntansha) KATAOKA Kazunori  The University of Tokyo, Materials Science, Professor, 大学院・工学系研究科, 教授 (00130245)
筒井 宣政  株式会社東海メディカルプロダクツ, 代表取締役
加藤 政雄  東京理科大学, 基礎工学部, 教授 (70214400)
筒井 宜政  (株)東京メディカルプロダクツ, 代表取締役
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1998: ¥4,400,000 (Direct Cost: ¥4,400,000)
KeywordsPOLY(HEMA) / POLY(ETHYLENE GLYCOL) / BLOCK COPOLYMER MICELLE / SURFACE MODIFICATION AGENTS / HIGH DENSITY TETHERED CHAIN / BIOCOMPATIBLE SURFACE / DDS / NON-FOULING SURFACE / ポリ(メタクリル酸2-ヒドロキシエチル) / アニオン重合 / セミテレケリックス / ポリヒドロキシエチルメタクリレート / 血液適合性 / ぬれ
Research Abstract

We have synthesized seceral types of hydrophilic-hydrophobia block copolymers which forms supramolecular nanostructure in aqueous media due to the self-assembly of the block copolymers. For example, poly(ethylene glycol)/poly(lactide) block copolymer forms spherical core-shell type polymeric micelle in aqueous media, the size of which was 20-40 nm. The shell of the micelle was constructed by tethered PEG chains, whose density was very high in principle because of the thermodynamic balance.
The objective of our study was to construct polymer micelle covered surface. If the surface was covered by spherical polymer micelles densely, the density of tethered chains should be much higher that conventional brushed chain surface.
We prepared two types of polymer micelle. One of them is poly(2-hydroxyethyl methacrylate)-b-poly(alkylsilylstyrene) (HA) block copolymer micelle. By casting this polymer micelle on the substrate surface, the micelle adsorbed on the surface densely. Platelet adhesion to the modified surface was investigated. The adhesion on the HA-micelle modified surface was mush suppressed than that of not only native substrate but also poly(HEMA) surface. Entropy elastic effect of dense tethered chain may be the reason for this phenomena.
Alternately, PEG/PLA block copolymers possessing aldehyde group at PEG chain end and methacryloyl group at PLA chain end was prepared. The block copolymer in aqueous media forms core shell type polymer micelle possessing aldehyde groups on the surface. The methacryloyl group in the core could be polymerized radically to form non dissociative micelle. To a primary-amino containing substrate surface, the aldehyde-micelle was modified covalently via reductive amination reaction. The obtained surface was very dence in polymer micelle and extremely high non-fouling character.
These types of highly tethered chain surface was anticipating as new biocompatible surface modification agents.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] 長崎幸夫: "Block Copolymer Micelles for Drug Delivery : Design, Characterization and Biological Significance"Advanced Drug Delivery Review. 47/1. 113-131 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 長崎幸夫: "Functionality of Polymeric Micelle Hydrogel with Organized Three Dimensional Architecture on Surfaces"Journal of Americal Chemical Society. 122/11. 2653-2654 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 長崎幸夫: "Selective Synthesis of Heterobifunctional Poly (ethylene glycol) Derivatives Containing Both Mercapto and Acetal Terminals"Bioconjugate Chemistry. 11/6. 947-950 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 長崎幸夫: "Preparation of non-fouling surface through the coating with core-polymerized block copolymer micelles having aldehyde-ended PEG shell"Colloids and Surfaces B : Biointerfaces. 18/3/4. 337-346 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 長崎幸夫: "A Core-Shell Structured Hydrogel Thin Layer on Surfaces by Lamination of a Poly (ethylene glycol)-b-poly (d, l-lactide Micelleand Polyallylamine"Langmuir. 16/13. 5738-5742 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 長崎幸夫: "Stimuli-Sensitive Polymer Gels That Stiffen upon Swelling"Macromolecules. 33/14. 4992-4994 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 長崎幸夫: "Novel Approaches for hte Construction of Functionalized PEG Layer on Surface Using Heterobifunctional PEG-PLA Block Copolymers and Their Micelles (764)"American Chemical Society. 17 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 長崎幸夫: "微粒子・粉体の最先端技術"シー・エム・シー. 11 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazunori Emoto, Yukio Nagasaki, Michihiro Iijima, Masao Katoa, Kazunori Kataoka: "Preparation of non-fouling surface through the coating with core-polymerized block copolymer micelles having aldehyde-ended PEG shell"Colloids and Surfaces B : Biointerfaces. Vol.18(3/4). 337-346 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukio Nagasaki, Hidetoshi Aoki: "Poly(siloxyethylene glycol) for New Functionality Materials in "Silicon and Silicone-Modified Materials" ed by Stephen L.Clason"American Chemical Society, Symposium. Series 729. 359-382 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirakawa, Takashi Tokuda, Hidetoshi Aoki, Yukio Nagasaki, Masao Kato: "Dry-Developable Electron Beam Resist -Synthesis and Resist Characteristic Evaluation of Amino-ended Poly(a-Methylstyrene)-"Journal of Photopolymer Science and Technology. Vol.13(2). 211-212 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshitsugu Akiyama, Atsushi Harada, Yukio Nagasaki, Kazunori Kataoka: "Synthesis of Poly(ethylene glycol)-block-poly(ethylene imine) possessing an acetal group at PEG end"Macromolecules, Communication to the Editor. Vol.33(16). 5841-5845 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] LaiBin Luo, Masao Kato, Teiji Tsuruta, Kazunori Kataoka, Yukio Nagasaki: "Stimuli-Sensitive Polymer Gels That Stiffen upon Swelling"Macromolecules, Communication to the Editor. Vol.33(14). 4992-4994 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazunori Emoto, Yukio Nagasaki, Kazunori Kataoka: "A Core-Shell Structured Hydrogel Thin Layer on Surfaces by Lamination of a Poly(ethylene glycol)-b-poly(d, l-lactide Micelleand Polyallylamine"Langmuir. Vol.16(13). 5738-5742 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazunori Emoto, Michihiro Iijima, Yukio Nagasaki, Kazunori Kataoka: "Functionality of Polymeric Micelle Hydrogel with Organized Three Dimensional Architecture on Surfaces"Journal of American Chemical Society. Vol.122(11). 2653-2654 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hidenori Otsuka, Yukio Nagasaki, Kazunori Kataoka: "Surface Characterization of Functionalized Polylactide through the Coating with Heterobifunctional Poly(ethylene glycol)/Polylactide Block Copolymers"Biomacromolecules. Vol.1(1). 39-48 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hidenori Otsuka, Yoshikazu Nakashima, Yukio Nagasaki, Masao Kato, Kazunori Kataoka: "Novel Approaches for The Construction of Celle Specific Surfaces using Heterobifunctional Poly(ethylene glycol)"Journal of Photopolymer Science and Technology. Vol.13(1). 25-28 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hidenori Otsuka, Yukio Nagasaki, Kazunori Kataoka: "SDynamic Wettability Study on the Functionalized PEGylated Layer on a Polylactide Surface Constructed by the Coating of Aldehyde-ended Poly(ethylene glycol) (PEG)/polylactide (PLA) Block Copolymer"Science and Technology of Advanced Materials. Vol.1. 21-29 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koji Tsuruhara, Masahiro Rikukawa, Kohei Sanui, Naoya Ogata, Yukio Nagasaki, Masao Kato: "Synthesis of protom conducting polymer based on Poly(silamine)"Electrochimica Acta. Vol.45. 1391-1394 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 長崎幸夫: "Block Copolymer Micelles for Drug Delivery : Design, Characterization and Biological Significance"Advanced Drug Delivery Review. 47/1. 113-131 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長崎幸夫: "Functionality of Polymeric Micelle Hydrogel with Organized Three Dimensional Architecture on Surfaces"Journal of Americal Chemical Society. 122/11. 2653-2654 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長崎幸夫: "Selective Synthesis of Heterobifunctional Poly (ethylene glycol) Derivatives Containing Both Mercapto and Acetal Terminals"Bioconjugate Chemistry. 11/6. 947-950 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長崎幸夫: "Preparation of non-fouling surface through the coating with core-polymerized block copolymer micelles having aldehyde-ended PEG shell"Colloids and Surfaces B : Biointerfaces. 18/3/4. 337-346 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長崎幸夫: "A Core-Shell Structured Hydrogel Thin Layer on Surfaces by Lamination of a Poly (ethylene glycol)-b-poly (d,1-lactide Micelleand Polyallylamine"Langmuir. 16/13. 5738-5742 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長崎幸夫: "Stimuli-Sensitive Polymer Gels That Stiffen upon Swelling"Macromolecules. 33/14. 4992-4994 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長崎幸夫: "Novel Approaches for hte Construction of Functionalized PEG Layer on Surface Using Heterobifunctional PEG-PLA Block Copolymers and Their Micelles"American Chemical Society. 17 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長崎幸夫: "微粒子・粉体の最先端技術"シー・エム・シー. 11 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長崎幸夫: "Network Formation of Poly(ehtykene glycol)-b-Poly(D,L lactide) Micelle with Polyallyl amine on Surface"Journal of American Chemical Society,. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 長崎幸夫: "Surface Characterization of Functionalized Polylactide through the Coating with Heterobifunctional Poly(ehtykene glycol)/Polylactide Block Copolymers"Biomacromolecules. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 長崎幸夫: "Polyion Complex Micelles with Reactive Aldehyde Groups on Surface from Plamid DNA and End-Functionalized Charged Block Copolymers"Macromolecules,Communication to the Editor. 32. 6892-6894 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 長崎幸夫: "Coating of Surfaces with Stabilized Reactive Micelles from poly (ehtykene glycol)-Poly (DL- lactic acid)block Copolymer"Langmuir. 15. 5212-5218 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 長崎幸夫: "Preparation and characterization of polymer micells from poly (ehtykene glycol)-Poly (d,l- lactide)block copolymer as potential drug carrier"Journal of Controlled Release. 62. 89-100 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 長崎幸夫: "Core-Polymerized Reactive Micelles from Heterotelechelic Amphiphilic Block Copolymers"Macromolecules. 32. 1140-1146 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 長崎幸夫: ""Molecular Design for A New Positive Electron-Beam Resis",in "Micro-and Nanopatterning Polymers""ACS Symposium Series,Washington,D.C.,706,pp.276-289(1999). 14 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 長崎幸夫: "The "Reactive Polymeric Micelle",Convenient Tool for Targetting Drug Delivery System in "Materals for Controlled Release Applications""ACS Symposium Series,Washington,D.C.,pp.105-116(1998). 12 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Nagasaki: "Core-polymerized reactive micelles from heterotelechelic amphiphilic block copolymers" Macromolecules. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagasaki: "Preparation anda characterization of polymer micelles form poly(ethylene glycol)-poly(d,I-lactide)block copolymer as potential drug carrier" J.Controlled Release. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagasaki: "2-Phenylallyl-ended poly(a-methylstyrene)derivatives for electron bram resist" J.Photopolymer Science and Technology,Communication. 11(1). 163-164 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagasaki: "The reactive polymeric micelles based on an aldehyde-ended poly(ethyleneglycol)/poly(lactide)block copolymer" Macromolecules. 31(5). 1473-1479 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagasaki: "Synthesis of heterobifunctional poly(ethylene glycol)with a reducing monosaccharide residue at one end" Bioconjugate Chemistry,Technical Note. 9(2). 300-303 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagasaki: "Minimized platelet interaction with poly(2-hydroxyethy methacrylate)-block-poly(4-bis(trimethylsilyl)methylstyrene)hydrogel showing anomalously high free water content" J.Biomaterials Science,Polymer Ed.9(2). 111-130 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagasaki: "The“Reactive Polymeric Micelle"Convenient Tool for Targetting drug Delivery System" ACS Symposium Series,Washington,D.C., 105-116 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagasaki: "Poly(ethylene glycol)-based micelles for drug delivery" American Chemical Society,Washington,D.C., 11-20 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2024-08-29  

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