LIPOSOMAL GOLD COMPOUNDS\IMPROVED ANTIARTHRITIC THERAPY

CONJUGATED GOLD COMPOUNDS SUCH AS AUROTHIOMALATE, ARE ADMINISTERED IN PROGRESSIVE RHEUMATOID ARTHRITIS. AT PRESENT, ONLY THESE ANTIARTHRITICS ARREST THE PROGRESSION OF THE DISEASE. TREATMENT IS LIMITED BECAUSE SEVERE ORGAN TOXICITIES OCCUR IN 33% OF PATIENTS TAKING PARENTERAL OR ORAL GOLD COMPOUNDS. IT IS PROPOSED THAT AUROTHIOMALATE OR AUROTHIOGLUCOSE ENCAPSULATED INTO THE INTERNAL AQUEOUS SPACE OF UNILAMELLAR PHOSPHOLIPIDS VESICLES (LIPOSOMES) WOULD BE A MORE EFFECTIVE FORM OF THE DRUG BECAUSE TOXICITY WOULD BE REDUCED. IT IS FURTHER PROPOSED THAT THE DRUG WOULD BE DELIVERED TO LYMPHOCYTES FOUND IN THE SYNOVIUM AND INHIBIT THE PRODUCTION OF INFLAMMATORY MEDIATORS BY THESE CESS. THIS STUDY WILL INVOLVE THE PREPARATION OF GOLD COMPOUNDS INTO SMALL UNILAMELLAR VESICLES, EVALUATION OF THESE FORMULATIONS FOR STABILITY AND IN VITRO ACTIVITY, AND TESTING OF APPROPRIATE FORMULATIONS IN TYPE II COLLAGEN INDUCED ARTHRITIS MODEL IN MICE. DEVELOPMENT OF THIS DRUG DELIVERY SYSTEM WOULD EXTEND VESTAR'S TECHNOLOGY BASE BY THE DEVELOPMENT OF A LIPOSOME DRUG DELIVERY SYSTEM FOR WATER SOLUBLE ANTIINFLAMMATORY AGENTS.