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j.jconrel.2014.09.011.pdf | 1 MB | Adobe PDF | 見る/開く |
タイトル: | Self-assembling lipid modified glycol-split heparin nanoparticles suppress lipopolysaccharide-induced inflammation through TLR4-NF-κB signaling. |
著者: | Babazada, Hasan Yamashita, Fumiyoshi https://orcid.org/0000-0002-3503-8696 (unconfirmed) Yanamoto, Shinya Hashida, Mitsuru |
著者名の別形: | 橋田, 充 |
キーワード: | Inflammation Heparin nanoparticles Toll-like receptors Desulfation Macrophage Nuclear factor-κB |
発行日: | 28-Nov-2014 |
出版者: | Elsevier BV |
誌名: | Journal of controlled release |
巻: | 194 |
開始ページ: | 332 |
終了ページ: | 340 |
抄録: | Self-assembling heparin nanoparticles have attracted much attention as promising drug carriers for various drugs, genes and imaging agents. In the present investigation, we found that heparin nanoparticles are selective Toll-like receptor 4 (TLR-4) antagonists and have a much greater anti-inflammatory effect than native heparin. More specifically, we developed self-assembling nanoparticles composed of glycol-split heparin/d-erythro-sphingosine conjugates (NAHNP), characterized their physicochemical properties and anti-inflammatory effect in vitro. Unlike native heparin, NAHNP significantly inhibited lipopolysaccharide-induced activation of MyD88-dependent NF-κB signaling pathway and production of pro-inflammatory cytokines such as TNF-alpha from mouse macrophages with IC50=0.019mg/mL. Furthermore, we investigated the structure-activity relationship of the conjugates and identified the length of attached alkyl chains of d-erythro-sphingosine to be critical for anti-inflammatory effect. Decrease in alkyl chain length of NAHNP resulted in loss of inhibitory activity. In line with these findings, 6-O-sulfate groups of d-glucosamine residue were essential for effective inhibition, while removal of 2-O-sulfo and 3-O-sulfo groups as well as replacement of N-sulfo groups with N-acetyl did not alter anti-inflammatory activity. Therefore, NAHNP would be a promising candidate in acute and chronic inflammatory disorders, in addition to the nature of a drug carrier. |
著作権等: | © 2014 Elsevier B.V. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/191264 |
DOI(出版社版): | 10.1016/j.jconrel.2014.09.011 |
PubMed ID: | 25234820 |
出現コレクション: | 学術雑誌掲載論文等 |
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