Intra-articular Retention and Anti-arthritic Effects in Collagen-Induced Arthritis Model Mice by Injectable Small Interfering RNA Containing Hydrogel
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- Kanazawa Takanori
- School of Pharmacy, Nihon University School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Tamano Kuniko
- School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Sogabe Kana
- School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Endo Takahiro
- School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Ibaraki Hisako
- School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Takashima Yuuki
- School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Seta Yasuo
- School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Abstract
<p>Small interfering RNAs (siRNAs) are expected to offer a means of treating rheumatoid arthritis (RA) because they allow the specific silencing of genes related to RA pathogenesis. In our previous study, we reported that the siRNA targeted against RelA (anti-RelA siRNA), an important nuclear factor-kappaB (NF-κB) subdomain, was an effective therapeutic in atopic dermatitis and RA model animals. In this study, to develop an intra-articular injectable gel formulation against RA, we prepared a hydrogel that contains anti-RelA siRNA, and determined the in vitro release profile (%) and in vivo intra-articular retention of fluorescence-labeled model siRNA, and the anti-arthritic effects of the anti-RelA siRelA containing hydrogel in RA model mice. We selected the silk protein, sericin (SC), as an aqueous gel base, as it is a biocompatible and useful for forming hydrogels without a cross-linker. We showed that fluorescence-labeled model siRNA was continuously released from SC hydrogel in vitro, and retained in the knee joint of rats after injection of siRNA hydrogel. In addition, the knee joint thickness, clinical severity and incidence (%) in collagen-induced arthritis (CIA) mice as RA model treated with anti-RelA siRNA containing hydrogel were more improved than untreated, anti-RelA siRNA solution and negative control siRNA containing hydrogel group. Therefore, the intra-articular injectable sericin hydrogel formulation containing of anti-RelA siRNA could be a great potential therapeutic in rheumatoid arthritis.</p>
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 40 (11), 1929-1933, 2017
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390001204634514560
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- NII Article ID
- 130006191963
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 028602229
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- PubMed
- 29093340
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed