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

• Published in: The journal of gene medicine 2009-01, Vol.11 (1), p.26-37
• Main Authors: Kim, Sung Tae, Lee, Kyung-Mi, Park, Hyun-Joo, Jin, Su-Eon, Ahn, Woong Shick, Kim, Chong-Kook
• Format: Article
• Language: English
• Subjects: Administration, Topical; Animals; antisense oligonucleotide; atopic dermatitis; cationic elastic liposome; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - immunology; Gene therapy; Humans; interleukin-13; Interleukin-13 - antagonists & inhibitors; Interleukin-13 - genetics; Interleukin-4 - immunology; Interleukin-5 - immunology; Liposomes - chemistry; Mice; Mice, Inbred BALB C; NIH 3T3 Cells; Oligonucleotides, Antisense - administration & dosage; Tumor Cells, Cultured
• ISSN: 1099-498X; 1521-2254
• DOI: 10.1002/jgm.1268

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 Il‐13. Copyright © 2008 John Wiley & Sons, Ltd.