| Item type |
文献 / Documents(1) |
| 公開日 |
2022-07-26 |
| アクセス権 |
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|
アクセス権 |
open access |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
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|
関連識別子 |
https://doi.org/10.1016/j.jconrel.2022.01.052 |
|
|
関連名称 |
10.1016/j.jconrel.2022.01.052 |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| タイトル |
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|
タイトル |
Iontophoresis-mediated direct delivery of nucleic acid therapeutics, without use of carriers, to internal organs via non-blood circulatory pathways |
| 著者 |
Hasan, Mahadi
福田, 達也
イノウエ, シンヤ
モリ, ヒナコ
カガワ, マユコ
小暮, 健太朗
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| 抄録 |
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|
内容記述 |
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. |
| キーワード |
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|
主題 |
Drug delivery |
| キーワード |
|
|
主題 |
Iontophoresis |
| キーワード |
|
|
主題 |
Nucleic acid therapeutics |
| キーワード |
|
|
主題 |
siRNA |
| キーワード |
|
|
主題 |
Liver diseases |
| 書誌情報 |
en : Journal of Controlled Release
巻 343,
p. 392-399,
発行日 2022-02-04
|
| 収録物ID |
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|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
01683659 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA10458678 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA1153173X |
| 出版者 |
|
|
出版者 |
Elsevier |
| 権利情報 |
|
|
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/ |
| EID |
|
|
識別子 |
386961 |
| 言語 |
|
|
言語 |
eng |
jcr_343_392.pdf (1.34 MB)
