Abstract
The small interfering RNA (siRNA) is suggested to offer a novel means of treating atopic dermatitis (AD) because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB) subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC), which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA.
Highlights
Atopic dermatitis (AD) is a chronic inflammatory disease of the skin with a complex pathogenesis that is associated with both genetic and environmental factors [1]
Mice treated with FAM-small interfering RNA (siRNA) containing functional peptides, showed the presence of FAM-siRNA in the skin and the strongest FAM-siRNA fluorescence was observed in the dermis of the mice treated with siRNA/Tat + AT1002
We found that the siRNA was more widely delivered to the site of application in atopic dermatitis (AD)-induced ear skin of mice after topical application via the hydrogel with functional peptides than via the preparation without functional peptides
Summary
Atopic dermatitis (AD) is a chronic inflammatory disease of the skin with a complex pathogenesis that is associated with both genetic and environmental factors [1]. We found that the use of functional peptides, such as cell-penetrating or tight junction opening peptides to deliver the anti-RelA siRNA or RNAi reagents, was an effective therapeutic in a mouse model of AD [6,7]. We previously reported the silk protein SC as a useful biocompatible biomaterial for the formation of hydrogels without crosslinkages, as an aqueous gel base [25,26]. This versatile property made SC a suitable choice. We determined the intradermal permeation of fluorescencelabeled siRNA as well as the anti-AD effects of an anti-RelA siRNA preparation in different hydrogel formulations following topical skin application in an AD mouse model
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