Anti-RelA siRNA-Encapsulated Flexible Liposome with Tight Junction-Opening Peptide as a Non-invasive Topical Therapeutic for Atopic Dermatitis

• Ibaraki Hisako

  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences

• Kanazawa Takanori

  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences School of Pharmacy, Nihon University

• Kurano Takumi

  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences School of Pharmacy, Nihon University

• Oogi Chihiro

  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences

• Takashima Yuuki

  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences

• Seta Yasuo

  School of Pharmacy, Tokyo University of Pharmacy and Life Sciences

抄録

Small interfering RNA (siRNA) has been proposed as a novel treatment for atopic dermatitis (AD) because it suppresses sequence-specific mRNA expression. Indeed siRNA-based therapy achieves an almost complete cure with fewer side effects than currently available treatments. However, the tight junctions in the granular layer of the epidermis in the atopic skin are barriers to siRNA delivery. We previously reported the potential clinical utility of AT1002, a peptide that opens tight junctions. In the present study, we evaluated a topical siRNA-based therapy for AD using AT1002 in combination with a flexible liposome. The 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)/cholesteryl hemisuccinate (CHEMS) liposome was chosen as a carrier for siRNA because of its highly flexible structure and permeability. We prepared siRNA-encapsulated DOPE/CHEMS liposomes and examined their physical properties, safety, uptake into RAW264.7 cells, and topical application in healthy and AD-affected skin. We then assessed the efficacy of anti-nuclear factor-kappa B (NF-κB) (RelA) siRNA (siRelA)-encapsulated DOPE/CHEMS liposomes with AT1002 in AD model mice. The siRNA-DOPE/CHEMS liposomes were absorbed significantly better than siRNA alone and they enhanced siRNA skin penetration without toxicity. Moreover, siRelA-DOPE/CHEMS liposomes with AT1002 alleviated AD symptoms and reduced the levels of inflammatory cytokines in AD model mice. Therefore, the combination of AT1002 and DOPE/CHEMS liposomes could be a dermally applied RNA interference therapeutic system for effective RNA delivery and AD treatment.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 42 (7), 1216-1225, 2019-07-01

  公益社団法人 日本薬学会

キーワード

• atopic dermatitis
• small interfering RNA (siRNA)
• RelA
• topical siRNA application
• liposome
• AT1002 peptide

詳細情報

• CRID: 1390845713080230912
• NII論文ID: 130007672181
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b19-00259
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 029761981
• PubMed: 31257297
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I029761981
• Web Site: https://www.jstage.jst.go.jp/article/bpb/42/7/42_b19-00259/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2020109272
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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