Wunder, Andreas and Mueller-Ladner, Ulf and Stelzer, Ernst H. K. and Funk, Juergen and Neumann, Elena and Stehle, Gerd and Pap, Thomas and Sinn, Hannsjörg and Gay, Steffen and Fiehn, Christoph (2003) Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. JOURNAL OF IMMUNOLOGY, 170 (9). pp. 4793-4801. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)Abstract
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 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 likely due to effects on synovial fibroblasts, which might increase therapeutic efficacy and reduce side effects of MTX.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FIBROBLAST-LIKE SYNOVIOCYTES; COLLAGEN-INDUCED ARTHRITIS; LOW-DOSE METHOTREXATE; SYNOVIAL FIBROBLASTS; BEARING RATS; PHARMACOKINETICS; CONJUGATE; EXPRESSION; PROTEINS; MOUSE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2021 10:01 |
| Last Modified: | 13 Sep 2021 10:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39058 |
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