Silver Sulfadiazine (SSD) is the most widely used topical antimicrobial agent in the world and while effective against a wide variety of pathogens, i has been shown to delay wound healing. Formulation of SSD into creams and gels with the inclusion of a naturally-occurring component additive has been shown to significantly lower the toxicity of the formulation, improve the solubility of SSD, and improve the efficacy of the drug against several leading burn pathogens. The major specific aims of the proposed research involve the preparation & formulation/processing of the SSD in cream and gel formulations with varying concentrations of the naturally-occurring additive, determination of antimicrobial efficacy, 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 inflammation. This innovative and rational approach to an improved topical antimicrobial therapy is founded on the basis of several different studies that have revealed promising bioapplicable attributes of this improved and commonly applied therapy. 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.
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. Antimicrobial creams and gels using a well-known and controversial antimicrobial compound formulated to minimize toxicity so as to not delay healing, provide good efficacy against relevant burn pathogens, maintain soothing and hydrating properties, remain cost effective, and easy to clean from the patient is proposed as a solution to the aforementioned complications of burn injury.
Project Terms: Accounting; Acetates; Aging; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics; antimicrobial; antimicrobial drug; Antioxidants; Bacitracin; Bacteria; Bacteriology; base; Biological Assay; biomaterial compatibility; Burn injury; Cessation of life; Chemicals; Chronic Disease; Complex; Complication; cost effective; Cream; cytotoxicity; Dermal; Development; Diabetes Mellitus; drug development; drug efficacy; Drug Formulations; Drug usage; Effectiveness; Erythema; Evaluation; falls; FDA approved; Fibroblasts; Funding; Gel; Goals; Granulation Tissue; Healed; healing; Histocompatibility; Human; Hydrogels; Impaired wound healing; improved; In Vitro; in vivo; Industry; Infection; Inflammation; innovation; Investments; keratinocyte; Klebsiella pneumonia bacterium; Ligands; Measurement; Metals; microbial; Microbial Biofilms; microbicide; Microcirculation; Modeling; Mupirocin; Neomycin; novel; Ointments; Oxidative Stress; pathogen; Patients; Peroxidases; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Polymyxin B; Preparation; prevent; Prevention; Process; Property; Pseudomonas aeruginosa; public health relevance; Rattus; Reaction; Reduced Glutathione; Research; research and development; research study; Resistance; Resolution; scale up; Sepsis; Silver; Sodium Chloride; Solubility; Solutions; Sterile coverings; success; Sulfadiazine; Sulfonamides; Surface; Technology; Testing; Thick; Time; Tissues; Topical agent; Topical Antibiotic; Toxic effect; wound; Wound Infection; Wounds and Injuries
