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A simple,noninvasive and efficient method for transdermal delivery of siRNA
Authors:Chang-Min Lin  Keng Huang  Yang Zeng  Xian-Cai Chen  Sen Wang  Yu Li
Institution:(1) Department of Plastic and Reconstructive Surgery, Tissue Engineering Laboratory, First Affiliated Hospital, Shantou University Medical College, No. 57, ChangPing Road, ShanTou City, Guangdong Province, China;(2) Emergency Department, Second Affiliated Hospital, Shantou University Medical College, ShanTou City, China;(3) Department of Histology and Embryology, Shantou University Medical College, ShanTou City, China;
Abstract:Effective delivery of therapeutic agents is the most challenging hurdle in the use of RNA interference for research and in the clinic. Here, we assessed whether a short synthetic peptide, ACSSSPSKHCG (TD-1), could be transported through rat footpad (follicle-free) skin and efficiently deliver small interfering RNA (siRNA) to knock down a target gene. Fluorescence microscopy revealed that topical co-administration of FITC-labeled TD-1 and FAM-labeled siRNA distributed uniformly from the epidermis to the subcutaneous tissue of rat footpad skin. Transmission electron microscopy revealed the absence of cell–cell junctions and enlarged spaces between epithelial cells in the TD-1-treated footpad skin. TD-1 delivery of anti-GAPDH siRNA significantly reduced the level of GAPDH in 72 h. TD-1 can create a transient opening in non-follicle rat skin for delivery of siRNA and reveal a novel mechanism of transdermal delivery of TD-1 and siRNA into the epidermis for gene knockdown. The system might have potential for siRNA delivery in skin for drug therapy.
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