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Noninvasive delivery of siRNA and plasmid DNA into skin by fractional ablation: Erbium:YAG laser versus CO2 laser
Institution:1. Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan;2. Department of Dermatology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan;3. Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan;4. Department Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;5. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;6. Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan;7. Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Taoyuan, Taiwan;8. Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan;9. Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan;1. University of Greifswald, Department of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Greifswald, Germany;2. Physiolution GmbH, Greifswald, Germany;1. Sanofi-Aventis Deutschland GmbH, Chemical and Biotechnological Development (C&BD) Frankfurt Chemistry, Frankfurt, Germany;2. Sanofi-Aventis Deutschland GmbH, R&D, LGCR, Analytical Development, Frankfurt, Germany;3. Sanofi-Aventis Deutschland GmbH, R&D, LGCR, Pharmaceutical Operations, Frankfurt, Germany;4. Covance Laboratories, Alnwick, Northumberland, United Kingdom;1. Department of Pharmaceutics, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czech Republic;2. Clinic of Oral and Maxillofacial Surgery, University Hospital Brno, Brno, Czech Republic;3. Department of Maxillo-Facial Surgery, University Hospital Ostrava, Ostrava, Czech Republic;1. Department of Pharmaceutical Science, University of Michigan, Ann Arbor, MI, USA;2. Department of Pharmaceutical Technology, Gazi University, Etiler-Ankara, Turkey;3. Hospira, Inc., Lake Forest, IL, USA;4. TSRL, Inc., Ann Arbor, MI, USA;1. Technische Universität Braunschweig, Institute for Chemical and Thermal Process Engineering (ICTV), Braunschweig, Germany;2. Technische Universität Braunschweig, Institute for Pharmaceutical Technology, Braunschweig, Germany
Abstract: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/cm2 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 CO2 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.
Keywords:Fractional ablation  Er:YAG laser  siRNA  Plasmid DNA  Skin
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