Noninvasive delivery of siRNA and plasmid DNA into skin by fractional ablation: Erbium:YAG laser versus CO₂ laser

The present study was conducted to evaluate the impacts of fractional erbium (Er):YAG and CO2 lasers on skin permeation of small interfering (si)RNA and plasmid (p)DNA vectors. In vitro skin delivery was determined with a Franz diffusion cell. In vivo absorption was investigated by observing fluorescence and confocal microscopic imaging. Fractional laser-mediated ablation of the skin resulted in significant enhancement of dextran and siRNA penetration. Respective fluxes of dextran (10 kDa) and siRNA, which had similar molecular size, with Er:YAG laser irradiation at 5 J/cm 2 were 56- and 11-fold superior to that of intact skin. The respective permeation extents of dextran and siRNA by the CO2 laser at 4 mJ/400 spots were 42- and 12-fold greater than that of untreated skin. Fluorescence and confocal images showed increased fluorescence intensities and penetration depths of siRNA and pDNA delivery. According to an examination of the follicular permeant amount and fluorescence microscopy, hair follicles were important deposition areas for fractional laser-assisted delivery, with the Er:YAG modality revealing higher follicular siRNA selectivity than the CO 2 modality. This is the first report of siRNA and pDNA penetrating the skin with a sufficient amount and depth with the assistance of fractional lasers.