Project/Area Number |
11694129
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomedical engineering/Biological material science
|
Research Institution | The University of Tokyo |
Principal Investigator |
KATAOKA Kazunori Graduate School of Engineering, Professor, 大学院・工学系研究科, 教授 (00130245)
|
Co-Investigator(Kenkyū-buntansha) |
NAGASAKI Yukio Science University of Tokyo, Department of Materials Science, Associate Professor, 基礎工学部, 助教授 (90198309)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
|
Keywords | Block copolymer / Poly(ethylene glycol) / Polylactide / Polymeric micelle / Core-shell structure / Biocompatibility / Surface coating / Protein adsorption / コアーシェル型超微粒子 |
Research Abstract |
1) Nanostructure fabrication from block copolymers was carried out in this study. Particularly, novel approaches for the construction of functionalized poly(ethylene glycol) (PEG) layers on surfaces were focused to attain the specific adsorption of a target protein through a PEG-conjugated ligands with a minimal non-specific adsorption of other proteins. Further, surface organization of block copolymer micelles with cross-linking core was studied from a standpoint of the preparation of a new functional surface-coating with a unique macromolecular architecture. The micelle-attached surface and the thin hydrogel layer made by layered micelles exhibited nonfouling properties and worked as the reservoir for hydrophobic reagents. These PEG-functionalized surface in brush form or in micelle form can be used in diverse fields of medicine and biology to construct high-performance medical devices including scaffolds for tissue engineering and matrices for drug delivery systems. 2) Recently, coll
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oidal carrier systems have been receiving much attention in the field of drug targeting because of their high loading capacity for drugs as well as of their unique disposition characteristics in the body. This research project was aimed at the utility of polymeric micelles formed through the multimolecular assembly of block copolymers as novel core-shell typed colloidal carriers for drug and gene targeting. The process of micellization in aqueous milieu is studied in detail based on the differences in the driving force of core segregation, including hydrophobic interaction, electrostatic interaction, metal complexation, and hydrogen bonding of constituent block copolymers. The segregated core embedded in the hydrophilic palisade is shown to function as a reservoir for genes, enzymes, and a variety of drugs with diverse characteristics. Functionalization of the outer surface of the polymeric micelle to modify its physicochemical and biological properties is investigated from the standpoint of designing micellar carrier systems for receptor-mediated drug delivery. Further, the body distribution of polymeric micelles is studied to demonstrate their long-circulating characteristics and significant tumor accumulation, emphasizing their promising utility in tumortargeting therapy. As an important perspective on carrier systems based on polymeric micelles, their feasibility as nonviral gene vectors is also demonstrated in this study. Less
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