Item type |
文献 / Documents(1) |
公開日 |
2021-08-06 |
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 |
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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.ijpharm.2021.120601 |
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関連名称 |
10.1016/j.ijpharm.2021.120601 |
出版タイプ |
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出版タイプ |
AM |
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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 |
Overcoming thickened pathological skin in psoriasis via iontophoresis combined with tight junction-opening peptide AT1002 for intradermal delivery of NF-κB decoy oligodeoxynucleotide |
著者 |
福田, 達也
タナカ, ダイチ
イノウエ, シンヤ
ミチウエ, コウキ
小暮, 健太朗
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抄録 |
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内容記述 |
Transdermal delivery of nucleic acid therapeutics has been demonstrated to be effective for psoriasis treatment. We previously reported the utility of iontophoresis (IP) using weak electric current (0.3-0.5 mA/cm2) for intradermal delivery of nucleic acid therapeutics via weak electricity-mediated intercellular junction cleavage, and subsequent exertion of nucleic acid function. However, the thickened pathological skin in psoriasis hampers permeation of IP-administered macromolecules. Thus, approaches are needed to more strongly cleave intercellular spaces and overcome the psoriatic skin barrier. Herein, we applied a combination of tight junction-opening peptide AT1002 with IP, as synergistic effects of weak electricity-mediated intercellular junction cleavage and the tight junction-opening ability of AT1002 may help overcome thickened psoriatic skin and facilitate macromolecule delivery. Pretreatment with IP of an AT1002 analog exhibiting positively-charged moieties before fluorescence-labeled oligodeoxynucleotide IP resulted in the oligodeoxynucleotide permeation into psoriatic skin, whereas IP of the oligodeoxynucleotide alone did not. Moreover, psoriasis-induced upregulation of inflammatory cytokine mRNA levels was significantly suppressed by NF-κB decoy oligodeoxynucleotide IP combined with the AT1002 analog, resulting in amelioration of epidermis hyperplasia. These results suggest that synergistic effects of IP and an AT1002 analog can overcome thickened psoriatic skin and enable intradermal delivery of NF-κB decoy oligodeoxynucleotide for psoriasis treatment. |
キーワード |
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主題 |
Transdermal drug delivery |
キーワード |
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主題 |
Iontophoresis |
キーワード |
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主題 |
Nucleic acid therapeutics |
キーワード |
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主題 |
NF-κB decoy oligodeoxynucleotide |
キーワード |
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主題 |
AT1002 |
キーワード |
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主題 |
Psoriasis |
書誌情報 |
en : International Journal of Pharmaceutics
巻 602,
p. 120601,
発行日 2021-04-24
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収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
03785173 |
収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA00680771 |
収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA11530828 |
出版者 |
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出版者 |
Elsevier |
権利情報 |
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権利情報 |
© 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
EID |
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識別子 |
377805 |
言語 |
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言語 |
eng |