WE PROPOSE TO 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.

WE PROPOSE TO 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. IN PHASE I WE WILL INCREASE ENTRAPMENT OF GENTAMICIN IN LIPOSOMES AND CONDUCT RANGE-FINDING EFFICACY AND SAFETY STUDIES OF THE RESULTING PREPARATIONS. PHASE II WILL SCALE UP THE BEST LIPOSOME PREPARATION FROM PHASE I TO A PILOT FORMULATION, CONFIRM THE ORIGINAL ANIMAL STUDIES WITH THE SCALED-UP FORMULATION, INITIATE PHARMACEUTICAL STABILITY STUDIES, OBTAIN OCULAR TOXICITY PROFILE, MODIFY FORMULATION(S) AS NECESSARY TO REACH SATISFACTORY CLINICAL FORMULATION, AND PREPARE AN IND. WE WILL CONDUCT CLINICAL PHARMACOLOGY (PHASES I AND II) AND CLINICAL TRIALS (PHASE III) ON THE CLINICAL FORMULATION, AND PREPARE AND FILE THE NDA. 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 DECREASED TOTAL BODY EXPOSURE TO THE POTENTIAL TOXICITY OF AMINOGLYCOSIDES. THIS TECHNOLOGICAL INNOVATION RESULTS FROM ENHANCING THE ENTRAPMENT OF THE AMINOGLYCOSIDE ANTIBIOTIC, GENTAMICIN, BEYOND THE 14% REPORTED IN THE LITERATURE AND IN DEVELOPING A LIPOSOME FORMULATION PROVIDING CONTROLLED DRUG RELEASE WITH STABILITY EQUIVALENT TO OTHER COMMERCIALLY AVAILABLE PREPARATIONS.