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In vitro and in vivo characteristics of core–shell type nanogel particles: Optimization of core cross-linking density and surface poly(ethylene glycol) density in PEGylated nanogels
http://hdl.handle.net/2241/113921
http://hdl.handle.net/2241/113921c7678ac9-da76-4df1-a658-d1aab8b1c15b
名前 / ファイル | ライセンス | アクション |
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ActBio_7-9.pdf (620.9 kB)
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Item type | Journal Article(1) | |||||
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公開日 | 2011-09-15 | |||||
タイトル | ||||||
タイトル | In vitro and in vivo characteristics of core–shell type nanogel particles: Optimization of core cross-linking density and surface poly(ethylene glycol) density in PEGylated nanogels | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Tamura, Masato
× Tamura, Masato× Ichinohe, Satoshi× Tamura, Atsushi× Ikeda, Yutaka× Nagasaki, Yukio |
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著者別名 |
田村, 磨聖
× 田村, 磨聖× 長崎, 幸夫 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The biocompatibility and body distribution of PEGylated polyamine nanogels composed of chemically cross-linked poly(2-N,N-(diethylamino)ethyl methacrylate) (PEAMA) gel cores surrounded by poly(ethylene glycol) (PEG) chains were investigated to evaluate their feasibility as drug nanocarriers for systemic administration. PEGylated nanogels with different cross-linking densities (1, 2, and 5 mol.%) were prepared to evaluate their biocompatibilities by in vitro cytotoxicity assay, hemolysis assay, and in vivo acute toxicity assay. The toxic effect of the PEGylated nanogels derived from polyamine gel cores was significantly reduced when the cross-linking density was increased, and those with a cross-linking density of 5 mol.% showed a remarkably high median lethal dose (LD50) value >200 mg kg−1,despite the abundance of amino groups in the core. One hour after intravenous injection the PEGylated nanogels were found to have been eliminated from the systemic circulation, and less than 1% of the injected dose (ID) remained in the bloodstream. To improve the blood circulation time by increasing the surface PEG density of the PEGylated nanogels post-PEGylation of the PEGylated nanogels (via the Menschutkin reaction between tertiary amines of the PEAMA gel core and bromobenzyl-terminated short PEG) was carried out. A biodistribution study of these post-PEGylated nanogels revealed that the blood circulation time of the nanogels was definitely prolonged as the PEG content was increased. Therefore, the precise design of PEGylated nanogels with increased cross-linking densities in their polyamine gel cores and increased surface PEG densities seems promising for systemic applications. | |||||
書誌情報 |
Acta Biomaterialia 巻 7, 号 9, p. 3354-3361, 発行日 2011-09 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1742-7061 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA11976339 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 21664304 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.actbio.2011.05.027 | |||||
権利 | ||||||
権利情報 | © 2011 Acta Materialia Inc. NOTICE: this is the author's version of a work that was accepted for publication in Acta Biomaterialia. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Acta Biomaterialia, Vol.7 Issue 9, Pages:3354-3361. doi:10.1016/j.actbio.2011.05.027 |
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著者版フラグ | ||||||
値 | author | |||||
出版者 | ||||||
出版者 | Elsevier | |||||
URI | ||||||
識別子 | http://hdl.handle.net/2241/113921 | |||||
識別子タイプ | HDL |