title: Noninvasive approach for enhancing small interfering RNA delivery percutaneously.
abstract: BACKGROUND
  Topically applied small interfering RNA (siRNA) can be an effective treatment for skin disorders. Using noninvasive strategies can be a safe and effective siRNA-permeation-enhancement approach for facilitating skin delivery. It has been demonstrated that noninvasive approaches for enhancing siRNA transport provide some advantages, including enhanced storage stability, targeted delivery, improved permeability and increased bioavailability.
  
  
  METHODS
  This review describes recent developments using noninvasive approaches for siRNA absorption enhancement. This review systematically introduces the concepts and enhancement mechanisms of the techniques, highlighting the potential of these techniques for increasing gene absorption via the skin. These techniques include nanomedicine, penetration enhancers, matrix-based delivery, microneedles, iontophoresis, electroporation and lasers. These modalities are useful for enhancing the permeation of a wide variety of siRNA for treating skin cancers, gene-related diseases, immune-related diseases and cutaneous wounds.
  
  
  CONCLUSIONS
  The potential use of the noninvasive approaches affords a new treatment for topical siRNA application with significant efficacy. Further studies using a large group for humans or patients are needed to confirm and clarify the findings in animal studies. Although a safe and nontoxic outcome is claimed, the possible adverse effects and irritation elicited by the noninvasive techniques cannot be ignored.
authors.affiliation: a Department of Pharmaceutics , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Aljuffali
authors.affiliation: b School of Traditional Chinese Medicine , Chang Gung University , Kweishan , Taoyuan , Taiwan.|c Department of Traditional Chinese Medicine , Chang Gung Memorial Hospital at Keelung , Keelung , Taiwan.
authors.forename: Yin-Ku
authors.initials: YK
authors.lastname: Lin
authors.affiliation: d Pharmaceutics Laboratory, Graduate Institute of Natural Products , Chang Gung University , Kweishan , Taoyuan , Taiwan.|e Chinese Herbal Medicine Research Team, Healthy Aging Research Center , Chang Gung University , Kweishan , Taoyuan , Taiwan.|f Research Center for Industry of Human Ecology , Chang Gung University of Science and Technology , Kweishan , Taoyuan , Taiwan.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000279:Administration, Cutaneous; D016503:Drug Delivery Systems / Q000379:methods*; D018274:Electroporation; D006801:Humans; D007478:Iontophoresis; D007834:Lasers; D036103:Nanotechnology; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000502:physiology*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D034741:RNA, Small Interfering
keywords: Cutaneous delivery; noninvasive approach; percutaneous absorption; siRNA; skin