Three novel uncharged silver microbicides have been shown to be effective against a wide variety of pathogens have been shown to spontaneously form amorphous hydrogels when combined with glutathione will be formulated into two different ointment formulations and tested in an infected burn wound model in the rat. Formulation of the silver microbicides will be conducted at different concentrations for evaluation. The major specific aims of the proposed research involve the preparation & formulation/processing of the silver microbicides, determination of antimicrobial capacity, cyto-compatability, and evaluation in an infected burn wound model in the rat. The primary objectives of the proposed therapy are: 1) resolution of infection, 2) improvement of healing, and 3. reduction in overall oxidative stress. This innovative and rational approach to a topical antimicrobial therapy is founded on the basis of several different studies that have revealed promising bioapplicable attributes of these silver microbicide complexes. The end-goal of this project is to enable the next phase of development of one or more of these novel microbicidal formulations that will be targeted for the treatment of burn wounds while developing a greater understanding of the mechanisms by which these compounds work.
Public Health Relevance Statement: Public Health Relevance: Infection is the most common and most serious complication of a major burn injury. Despite improvements in burn wound management and antimicrobial therapy technologies, sepsis related to the burn accounts for 50-60% of deaths in burn patients today. Other complicating issues that hamper efficient healing include cellular oxidative stress, topical agent toxicity, and ease of patient treatment. An antimicrobial gel with minimal toxicity, good efficacy against relevant burn pathogens, anti oxidative characteristics, and soothing and hydrating properties, allows for easy visualization of the wound, and is easily cleaned from the patient is proposed as a solution to the aforementioned complications of burn injury.
NIH Spending Category: Bioengineering; Injury (total) Accidents/Adverse Effects
Project Terms: Accounting; Acetates; Animal Model; Antibiotics; antimicrobial; antimicrobial drug; Antioxidants; Bacteria; base; biomaterial compatibility; Burn injury; carbene; Cessation of life; Characteristics; Complex; Complication; Cream; Dermal; design; Development; Dose; Drug Formulations; Effectiveness; Environment; Erythema; Evaluation; Fibroblasts; Free Radicals; Gel; Glutathione; Goals; Granulation Tissue; Healed; healing; Histocompatibility; Hydrogels; Imagery; improved; In Vitro; in vivo; Individual; Infection; Inflammation; innovation; leukocyte activation; Light; Lipid Peroxidation; Lipids; Liquid substance; Maintenance; Measurement; Methicillin Resistance; microbial; Microbial Biofilms; microbicide; Modeling; Nature; novel; Ointments; Oxidative Stress; pathogen; Patients; Performance; Peroxidases; Phase; Preparation; Process; Production; programs; Property; protein complex; Pseudomonas aeruginosa; public health relevance; Rattus; Reactive Oxygen Species; Reduced Glutathione; Research; resistant strain; Resolution; Running; scale up; Sepsis; Silver; Solubility; Solutions; Staphylococcus aureus; Sterile coverings; Sulfadiazine; Technology; Testing; Therapeutic; Thick; Tissues; TNF gene; Topical agent; Topical Antibiotic; Toxic effect; Toxin; Treatment outcome; Work; wound; Wound Healing
