Develop a Gentamicin liposome controlled release formulation suitable for topical treatment of bacterial keratitis and conjunctivitis that provides efficacy and safety equal to or better than present therapy and which requires fewer doses. Phase I Goals: Increase entrapment of gentamicin in liposomes and conduct range-finding efficacy and safety studies of the resulting preparations. Phase II Goals: Scale-up the best liposome preparation from Phase I to a pilot formulation, confirm the original animal studies with the scaled-up formulation, initiate pharmaeutical stability studies, obtain ocular toxicity profile, modify formation(s) as necessary to reach satisfactory clinical formulation, and prepare and IND. Phase III Goals: Conduct clinical pharmacology (phases I and II) and clinical trials (phase III) on the clinical formulation, and prepared and file the DNA. Present topical therapies for bacterial keratoconjunctivitis require dosing up to every hour for 3 days. The reduced dosing innovation described here will result in increased compliance and decreated total body exposure to the potential toxicity of aminoglycosides. This technological innovation results from enhancing the entrapment of the aminoglycoside antibiotic, Gentamicin, beyond the 1-4% reported in the literature and in developing a liposome formulation providing controlled drug release with stability equivalent to other commercially available preparations.
