Atopic dermatitis (AD) is the most common type of eczema. The Th2 immune response seems to play a pivotal role in AD. This involves in Th2 cytokines such as IL-4 which share the IL-4Rα. Transdermal administration improves patient quality of life because of noninvasive; however, typical ASO and antibody drug delivery into the skin can be challenging owing to the barrier of tight junctions in the granular layer. Therefore, we aimed to develop a delivery system of ASO for topical application using our technology, POLIGOTM. POLIGOTM, which is based on PNA (Peptide Nucleic Acid) has the nanoparticle characters and is able to transdermal delivery without physical force (microneedle). We improved the PNA (high selectivity, stability, nanoparticle-characters) to overcome low selectivity and delivery using our technology. Our purpose was to evaluate the effects of POL201 (cream type of IL-4Rα targeted POLIGOTM) on dinitrochlorobenzene (DNCB) induced NC/Nga mice. We measured epidermis thickness, CD3, and CD11c expression of DNCB-induced AD mouse skin and the levels of IgE, IL-4, IL-13, and TARC in the serum by ELISA. Also, the effects of POL201 on expression level of IL-4Rα was evaluated in AD mouse skin. POL201 efficiently decreased the number of CD3/CD11c positive cells as well as thickness of the epidermis and dermis. The POL201 group significantly reduced serum level of IgE, IL-4, IL-13 and TARC. Moreover, IL-4Rα inhibited in the POL201 group compared with the DNCB-treated group. In addition, POL201 group showed that the clinical index, SCORAD (redness, scabs, itching and thickness) was dramatically improved than positive control (dexamethasone group). As the results, POL201 significantly inhibited AD pathogenesis and clinical index through reduction of IL-4Rα expression in AD animal model. Unlike conventional ASO treatments (subcutaneous injection), POL201 was able to deliver to the skin using cream formulation alone and inhibited the target gene IL-4Rα. Our results suggest that POL201 could be a potential therapeutic candidate for the treatment of AD.

IL-4Rα Targeted-POLIGOTM Cream Improves DNCB-Induced Atopic Dermatitis Mouse Model