| Project/Area Number |
09480253
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Japan Advanced Institute of Science and Technology |
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Principal Investigator |
YUI Nobuhiko School of Materials Science, Japan Advanced Institute of Science and Technology, Professor, 材料科学研究科, 教授 (70182665)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1997: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Polyrotaxane / Drug carriers / Supramolecular structure / Degradation / Hydrogel / Tissue regeneration / 組織再生 / 生体内分解性高分子 / 溶液構造 |
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| Research Abstract |
In this research, we have studied biodegradable polyrotaxanes as new biomaterials for the first time in the world. In detail, we designed biodegradable polyrotaxanes and clarified those specific characteristics including biodegradability and physical interaction with biological components.
We have synthesized a polyrotaxane in which many α-cyclodextrins (α-CDs) are threaded onto a poly (ethylene glycol)(PEG) chain capped with enzymatically hydrolyzable amino acid (L-phenylalanine) via peptide bonds. We have clarified that the polyrotaxanes form loosely packed association and maintain their rod-like structure in physiological conditions. In vitro degradation experiments revealed that the terminal hydrolysis by a proteinase is completed and accompanied by supramolecular dissociation due to the loosely packed association. Based on this characteristic, we have introduced a model drug (theophylline) into the α-CDs in the polyrotaxane to examine drug release via the supramolecular dissociatio
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n. The obtained drug-polyrotaxane conjugate formed a specific association under physiological conditions, depending on interactions between drugs and/or terminals of the polyrotaxane in the conjugate. From in vitro degradation tests, it was found that drug-immobilized α-CDs are completely released by hydrolysis of the terminal peptide linkages in the polyrotaxane without any steric hindrance. Further, we have synthesized oligopeptide-terminated polyrotaxanes and clarified complete hydrolysis and supramolecular dissociation in the presence of membrane-bound metalloexopeptidaase that hydrolyzes unlikely substrates with higher molecular weight. This result suggests that enzymatic recognition of the biodegradable moiety is maintained.
Another approaches to biodegradable polyrotaxanes have been focused for implantable materials. We have synthesized hydolyzable polyrotaxanes that contain ester linkages at the terminals and demonstrated complete-supramolecular dissociation via the terminal ester hydrolysis. This dissociation rate can be controlled by chemical modification such as acethylation of hydroxyl groups in the polyrotaxanes. By using the hydrolyzable polyrotaxanes, we designed supramolecular-structured hydrogels in which hydroxyl groups of α-CDs are cross-linked with another PEG.By changing molar ratio of α-CDs and PEG on the hydrogel preparation, erosion time and profile of the hydrogels can be controlled. From these results, we found that enhanced stability of ester hydrolysis in the hydrogels with highly water swollen state. Such an anomalous phenomenon maybe due to the structural characteristic of the polyrotaxanes : ester linkages may be included within the cavity of α-CDs.
Therefore, we could establish the design of biodegradable polyrotaxanes with some new functions in this research project. Less
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