ar810 ARJ Oral presentation <p>Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis</p> Wunder A Muller-Ladner U Stelzer E Neumann E Sinn H Gay S Fiehn C

Department of Radiochemistry and Radiopharmacology, German Cancer Research Center, Heidelberg, Germany

Department of Internal Medicine I, University of Regensburg, Regensburg, Germany

Cell Biophysics/Cell Biology Program, European Molecular Biology Laboratory Heidelberg, Heidelberg, Germany

WHO Collaborating Center for Molecular Bioliology and Novel Therapeutic Strategies for Rheumatic Disorders, University of Zurich, Zurich, Switzerland

Clinic of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

 Arthritis Res Ther <p>3<sup>rd</sup> World Congress of the Global Arthritis Research Network (GARN): International Arthritis Summit</p> Meeting abstracts <p>3<sup>rd</sup> World Congress of the Global Arthritis Research Network (GARN): International Arthritis Summit</p> Summit Hall at Sheraton Resorts in Miyazaki, Japan 14–17 September 2003 1478-6354 2003 5 Suppl 3 9 10.1186/ar810 12 9 2003

We reported recently that albumin is a suitable drug carrier for targeted delivery of methotrexate (MTX) to tumors. Due to pathophysiological conditions in neoplastic tissue, high amounts of albumin accumulate in tumors and are metabolized by malignant cells. MTX, covalently coupled to human serum albumin (MTX-HSA) for cancer treatment, is currently being evaluated in phase II clinical trials. Because the synovium of patients with rheumatoid arthritis (RA) shares various features observed also in tumors, albumin-based drug targeting of inflamed joints might be an attractive therapeutic approach. Therefore, the pharmacokinetics of albumin and MTX in a mouse model of arthritis was examined. Additionally, uptake of albumin by synovial fibroblasts of RA patients and the efficacy of MTX and MTX-HSA in arthritic mice were studied. The results show that, when compared with MTX, significantly higher amounts of albumin accumulate in inflamed paws, and significantly lower amounts of albumin are found in the liver and the kidneys. The protein is metabolized by human synovial fibroblasts in vitro and in vivo. MTX-HSA was significantly more effective in suppression of the onset of arthritis in mice than was MTX. In conclusion, albumin appears to be a suitable drug carrier in RA, most probably due to effects on synovial fibroblasts, which might increase the therapeutic efficacy of and reduce side effects of MTX.