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 inflanunatory 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 11 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.Awardee's statement of the potential commercial applications of the research:There is a large number of drugs available to treat rheumatoid arthritis ranging from aspirin-like compounds, and non-steroidal antiinflammatories, to antineoplastics and several conjugated gold compounds. Severe toxicity is associated with the use of antineoplastic drugs and gold compounds. Liposome encapsulated autothiomalate or aurothioglucose would provide immunosuppressive therapy of the gold compounds while reducing toxicity and enhancing efficacy of the drug. The opportunity to develop this type of therapy would extend Vestar's technology base and provide a therapeutic for an extremely large patient population.National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
