Bacterial keratitis accounts for the majority of all microbial corneal infections, and is one of the leading causes of vision loss worldwide. The prevalence of antibiotic-resistant strains of bacteria has increased over recent years, adding complexities to the management of keratitis. Because of their distinct mechanism of action, the development of resistance to antimicrobial peptides is extremely unlikely, giving them a clear advantage over conventional antibiotics. The overall long-term goal of this project is to develop a novel topical ophthalmic pharmaceutical effective in treating keratitis resulting from bacterial infections from a wide variety of organisms. Successful development of this product would result in a broad-spectrum antimicrobial at least as effective as the antibiotics currently available, which is less susceptible to the development of bacterial resistance. Initial investigation of several synthetic antimicrobial peptides has determined that these molecules are extremely potent biocidal agents in vitro against gram-positive and gram-negative bacteria, yeast, and fungi. In other organ systems, they have been shown to maintain their efficacy in the human disease state. It remains to be seen whether or not these peptides will be feasible for use in ophthalmic drug preparations. The purpose of this initial investigation is to determine the chemical and toxicological suitability of these molecules for use as potential antimicrobial ophthalmic solutions. The Specific Aims of Phase I are to 1): Conduct pre-formulation studies designed to develop suitable ophthalmic formulations containing 3 specific anti-microbial peptides; 2) Conduct cytotoxicity tests using peptide formulations using established in vitro assays for determination of potential corneal epithelial toxicity. 3) Determine the relative efficacy of peptide formulations in vitro against a variety of microorganisms identified as common ocular infectious agents, including clinical isolates known to be resistant to currently available antibiotics; and 4) Identify lead formulations for further development.
Thesaurus Terms: antibacterial agent, biotherapeutic agent, drug design /synthesis /production, eye agent, eye infection, keratitis, peptide cytotoxicity, dosage forms, drug resistance, drug screening /evaluation
