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含丝胶基水凝胶的功能性肽局部抗核因子-κB小干扰RNA治疗特应性皮炎

Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis.

作者信息

Kanazawa Takanori, Shizawa Yuki, Takeuchi Mayu, Tamano Kuniko, Ibaraki Hisako, Seta Yasuo, Takashima Yuki, Okada Hiroaki

机构信息

Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. ;

Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

出版信息

Pharmaceutics. 2015 Sep 7;7(3):294-304. doi: 10.3390/pharmaceutics7030294.

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.

摘要

小干扰RNA(siRNA)被认为是一种治疗特应性皮炎(AD)的新方法,因为它能够特异性沉默与AD发病机制相关的基因。在我们之前的研究中,我们发现针对重要的核因子κB(NF-κB)亚结构域RelA的siRNA与功能肽结合,在AD小鼠模型中显示出治疗效果。在本研究中,为了开发一种针对AD的局部皮肤应用药物,我们制备了一种含有抗RelA siRNA和功能肽的水凝胶,并在AD小鼠模型中测定了其皮内渗透和抗AD效果。我们选择了丝蛋白丝胶(SC),它是一种通用的生物相容性生物材料,用于制备水凝胶作为水性凝胶基质。我们发现,与不含功能肽的制剂相比,通过含有功能肽的水凝胶局部应用后,siRNA在AD诱导的小鼠耳部皮肤的应用部位更广泛地递送。此外,用含有抗RelA siRNA和功能肽的水凝胶治疗的AD诱导小鼠的耳部厚度和临床皮肤严重程度比用阴性siRNA制剂治疗的小鼠改善得更多。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9794/4588201/5ff50ed66e95/pharmaceutics-07-00294-g001.jpg

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