Noninvasive delivery of siRNA into the epidermis by iontophoresis using an atopic dermatitis-like model rat.
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.
Kigasawa
K
K
Graduate School of Life Science, Hokkaido University, Sapporo-City, Hokkaido 060-0812, Japan.
Kajimoto
K
K
Hama
S
S
Saito
A
A
Kanamura
K
K
Kogure
K
K
D000279:Administration, Cutaneous; D000818:Animals; D003876:Dermatitis, Atopic / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D018014:Gene Transfer Techniques; D007478:Iontophoresis / Q000379:methods*; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D012869:Skin Absorption / Q000187:drug effects / Q000235:genetics
D034741:RNA, Small Interfering; D010047:Ovalbumin