The goal of this program is to develop a topical pharmaceutical formulation containing an optimized drug candidate from the 5-(n-substituted)salicylanilide class of patented, Lipophilic, Antimicrobial, Anti-inflammatory Drugs (LAADs) for the treatment of Diabetic Foot Ulcer (DFU). The 5-(n-substituted)salicylanilides are unique in that they potently inhibit the growth of several Gram-positive and Gram-negative bacteria and inhibit both acute and chronic dermal inflammation. In addition, these compounds bind strongly to surface tissue such as skin exhibiting virtually no transdermal penetration into the systemic circulation. A topical pharmaceutical preparation containing an optimized 5-(n-substituted)salicylanilide is predicted to have utility in controlling the pathogenesis of DFU, which is exacerbated by dermal bacterial infections and inflammation. We are proposing to choose an optimized 5-(n-substituted)salicylanilide for the treatment of Diabetic Foot Ulcer based on in vitro evaluation of their antimicrobial activity, in vivo evaluation of their topical anti-inflammatory activity, and preliminary formulation studies to accessibility and compatibility with excipients and solubilizing agents. In Phase II we will develop an optimized topical 5-(n-substituted)salicylanilide formulation, determine long-term chemical, microbiological and physical stability, and complete safety and preliminary efficacy studies using models and dosage schemes required by the FDA for a topical pharmaceutical preparation.
In the United States roughly 16 million people suffer from diabetes, and of these 3.2 million progress to diabetic foot ulcer (DFU) costing approximately $2B/annum. Current therapies to treat the disease include systemic antibiotics which are dose limiting due to circulation problems. Clearly an effective topical anti-inflammatory/antibacterial treatment would address a need in this growing market.
