https://scholars.lib.ntu.edu.tw/handle/123456789/638267
標題: | Development of triamcinolone acetonide-hyaluronic acid conjugates with selective targeting and less osteoporosis effect for rheumatoid arthritis treatments | 作者: | Chen, Tzu Yang NENG-YU LIN Wen, Chih Hao Lin, Chih An Venkatesan, Parthiban Wijerathna, Prasanna Lin, Chung Yu Lai, Ping Shan |
關鍵字: | Hyaluronic acid | Poorly water-soluble corticosteroid | Rheumatoid arthritis | 公開日期: | 15-五月-2023 | 卷: | 237 | 來源出版物: | International Journal of Biological Macromolecules | 摘要: | Rheumatoid arthritis (RA) is a common systemic autoimmune disease in developed countries. In clinical treatment, steroids have been used as bridging and adjunctive therapy after disease-modifying anti-rheumatic drug administration. However, the severe side effects caused by the nonspecific targeting of organs followed by long-term administration have limited their usage in RA. In this study, poorly water-soluble triamcinolone acetonide (TA), a highly potent corticosteroid for intra-articular injection, is conjugated on hyaluronic acid (HA) for intravenous purposes with increased specific drug accumulation in inflamed parts for RA. Our results demonstrate that the designed HA/TA coupling reaction reveals >98 % conjugation efficiency in the dimethyl sulfoxide/water system, and the resulting HA-TA conjugates show lower osteoblastic apoptosis compared with that in free TA-treated osteoblast-like NIH3T3 cells. Furthermore, in a collagen-antibody-induced arthritis animal study, HA-TA conjugates enhanced the initiative targeting ability to inflame tissue and reduce the histopathological arthritic changes (score = 0). Additionally, the level of bone formation marker P1NP in HA-TA-treated ovariectomized mice (303.6 ± 40.6 pg/mL) is significantly higher than that in the free TA-treated group (143.1 ± 3.9 pg/mL), indicating the potential for osteoporotic reduction using an efficient HA conjugation strategy for the long-term administration of steroids against RA. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/638267 | ISSN: | 01418130 | DOI: | 10.1016/j.ijbiomac.2023.124047 |
顯示於: | 解剖學暨細胞生物學科所 |
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