Topical delivery of interleukin-13 antisense oligonucleotides with cationic elastic liposome for the treatment of atopic dermatitis

Sung Tae Kim, Kyung-Mi Lee, Hyun Joo Park, Su Eon Jin, Woong Shick Ahn, Chong Kook Kim

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29 Citations (Scopus)

Abstract

Background: Interleukin (IL)-13, overproduced in the skin of atopic dermatitis (AD), has been shown to play an essential role in the pathogenesis of the disease. Thus, inhibition of IL-13 production should provide a key step to alleviate disease conditions of the atopic skin. In the present study, IL-13 antisense oligonucleotide (ASO) was designed and formulated with cationic elastic liposome (cEL) to improve transdermal delivery. Methods: ASOs were generated against murine IL-13 mRNA (+4 to +23) and complexed with cEL. Physicochemical properties of IL-13 ASO/cEL complex were examined by DNA retardation and DNase I protection assay. An in vitro inhibition study was performed in T-helper 2 (Th2) cells and cytotoxicity was tested by the XTT assay. The in vivo effect of IL-13 ASO/cEL complex was tested in a murine model of AD. Results: In vitro, the IL-13 ASO/cEL complex showed dose- and ratio-dependent inhibition of IL-13 secretion in Th2 cells. At the IL-13 ASO/cEL ratio of 6, maximum inhibition of IL-13 secretion was observed. When applied to the ovalbumin-sensitized murine model of AD, topically administered IL-13 ASO/cEL complex dramatically suppressed IL-13 production (by up to 70% of the control) in the affected skin region. In addition, the levels of IL-4 and IL-5 were also significantly reduced. Moreover, IL-13 ASO/cEL-treated AD mice showed reduced infiltration of inflammatory cells into the epidermal and dermal areas, with concomitant reduction of skin thickness. Conclusions: These data suggests that IL-13 ASO/cEL complex can provide a potential therapeutic tool for the treatment of AD and also be applied to other immune diseases associated with the production of II-13.

Original languageEnglish
Pages (from-to)26-37
Number of pages12
JournalJournal of Gene Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - 2009 Jun 1

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Keywords

  • Antisense oligonucleotide
  • Atopic dermatitis
  • Cationic elastic liposome
  • Interleukin-13

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery
  • Medicine(all)

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