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ID 117237
著者
Hasan, Mahadi Tokushima University|Kanazawa University
福田, 達也 Tokushima University|Wakayama Medical University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Inoue, Shinya Tokushima University
Mori, Hinako Tokushima University
Kagawa, Mayuko Tokushima University
キーワード
Drug delivery
Iontophoresis
Nucleic acid therapeutics
siRNA
Liver diseases
資料タイプ
学術雑誌論文
抄録
Nanoparticle drug carriers have been employed to achieve systemic delivery of nucleic acid therapeutics, including small interfering RNA (siRNA); however, non-specific distribution and immune-related events often cause undesired adverse effects. Thus, there is a need for a new technology capable of specifically delivering nucleic acid therapeutics to desired sites. We demonstrated the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm2) as a local drug delivery technology. Our previous studies revealed that IP allows for transdermal permeation of nucleic acid therapeutics via induction of intercellular junction cleavage initiated by Ca2+ influx-mediated cellular signaling activation, and subsequent cytoplasmic delivery through a unique endocytosis process in both skin and other cells. Based on these findings, we hypothesized that IP may enable direct delivery of nucleic acid therapeutics to internal organs through non-blood circulatory pathways without the use of delivery carriers. Permeation of fluorescent-labeled nucleic acids administered via IP applied to the surface of the liver and pancreas was observed in both organs, but not with topical application. IP-mediated local delivery of siRNA into the liver and pancreas significantly suppressed target mRNA expression in each organ. Moreover, IP administration of therapeutic siRNA against the molecules responsible for liver steatosis and fibrosis significantly inhibited lipid accumulation and fibrotic hepatic damage in individual model mice. These findings suggest that IP may be a useful technology to directly deliver nucleic acid therapeutics to internal organs without use of drug delivery carriers via non-blood circulatory pathways.
掲載誌名
Journal of Controlled Release
ISSN
01683659
cat書誌ID
AA10458678
AA1153173X
出版者
Elsevier
343
開始ページ
392
終了ページ
399
発行日
2022-02-04
備考
論文本文は2023-02-04以降公開予定
権利情報
© 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
出版社版DOI
出版社版URL
言語
eng
著者版フラグ
その他
部局
薬学系