Graduate School of Life Science, Hokkaido University, Sapporo-City, Hokkaido 060-0812, Japan.
Int J Pharm. 2010 Jan 4;383(1-2):157-60. doi: 10.1016/j.ijpharm.2009.08.036. Epub 2009 Sep 2.
Topical application of siRNA to the skin should be an effective treatment for serious skin disorders, such as atopic dermatitis. However, it is difficult to introduce hydrophilic macromolecules, including siRNA, into the skin by conventional methods. For efficient delivery of siRNA, we examined an iontophoretic technique, since it is suitable for the delivery of charged molecules. Naked siRNA effectively accumulated in the epidermis (and not in the dermis) after iontophoretic delivery. In contrast, siRNA did not penetrate tape-stripped skin by passive diffusion. In a rat model of atopic dermatitis, skin was sensitized with ovalbumin to stimulate IL-10 mRNA expression as observed in skin lesions. Iontophoretic delivery of anti-IL-10 siRNA significantly reduced (73%) the level of IL-10 mRNA. In conclusion, we successfully delivered naked siRNA into the epidermis and concomitantly suppressed the expression of an endogenous immuno-regulatory cytokine.
将 siRNA 局部应用于皮肤应该是治疗严重皮肤疾病（如特应性皮炎）的有效方法。然而，通过传统方法将亲水性大分子（包括 siRNA）引入皮肤是困难的。为了有效递送 siRNA，我们研究了电渗技术，因为它适合于传递带电分子。电渗递送后，siRNA 可有效积聚在表皮（而不是真皮）中。相比之下，siRNA 不会通过被动扩散穿透胶带剥离的皮肤。在特应性皮炎的大鼠模型中，用卵清蛋白致敏皮肤以刺激皮肤损伤中观察到的 IL-10 mRNA 表达。电渗递送抗 IL-10 siRNA 可显著降低（73%）IL-10 mRNA 的水平。总之，我们成功地将裸 siRNA 递送至表皮，并同时抑制内源性免疫调节细胞因子的表达。
