Development of Iontophoresis Device for Plasmid DNA Transfection of Hypoxia Inducible Factor-1 to Improve Wound Healing

DESCRIPTION provided by applicant Impaired wound healing is an unfortunate consequence of diabetes It is also seen in the elderly as well as individuals taking steroid medication There is an urgent need for a therapy that will be safe effective and easy to apply to improve impaired wound healing The situation is most urgent for individuals with diabetes whose foot ulcers are the most frequent cause for lower extremity amputations in the United States This project will lead initially to the marketing of a treatment modality that will promote healing of diabetic foot ulcers It will be used for recalcitrant ulcers where healing is not progressing It can be used for other difficult wounds as well There is no effective treatment for such wounds at this time Our goal for this SBIR is to develop a novel robust transfection strategy using iontophoresis We have preliminary work showing that this can be effective Iontophoresis is performed using a low voltage to create an electrical current in tissue In our situation the negatively charged plasmid DNA is driven through the tissue from the anode to the cathode For Phase of this SBIR we will work with a group from Johns Hopkins University School of Bioengineering to optimize the electrode arrays and electrical parameters to achieve transfection suitable for improving wound healing In Phase we will assess the efficacy and safety of the approach in a porcine model Our group has shown that the transcription factor Hypoxia Inducible Factor HIF can improve wound healing DNA delivery of a peptide like HIF is necessary because simple application of peptide growth factors has not been effective because of poor absorption and because the peptides are rapidly destroyed by peptidases in the dermis The DNA plasmid delivery promotes continuous production of the peptide in the dermis to circumvent these delivery problems PUBLIC HEALTH RELEVANCE Development of Iontophoresis Device for Plasmid DNA Transfection of Hypoxia Inducible Factor to Improve Wound Healing Impaired wound healing is an unfortunate consequence of diabetes and a problem for the elderly Expression of the important transcription factor Hypoxia Inducible Factor HIF is reduced in the wounds of the aged and people with diabetes HIF orchestrates the mobilization and wound homing of endogenous progenitor cells Restoring HIF expression in animal models improves wound healing This project will lead to the marketing of a treatment modality that will promote wound healing by delivering the HIF using DNA plasmid vectors achieving transfection using iontophoresis