Alleviation of rheumatoid arthritis by cell-transducible methotrexate upon transcutaneous delivery

Sang Won Lee, Ji Hye Kim, Min Chan Park, Yong Beom Park, Wook Jin Chae, Tomohiro Morio, Dong Ho Lee, Sang Hwa Yang, Seung Kyou Lee, Soo Kon Lee, Sang Kyou Lee

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Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is initiated and maintained by various inflammatory/immune cells and their cytokines, leading to cartilage degradation and bone erosion. Despite its potent therapeutic efficacy on RA, the oral administration of methotrexate (MTX) provokes serious adverse systemic complications, thus necessitating the local application of MTX. Here, we show that transcutaneous MTX (TC-MTX) can efficiently penetrate joint skin ex vivo and in vivo, and that TC-MTX can significantly improve the various inflammatory symptoms associated with RA. Further, TC-MTX preserved the joint-structures in mice with collagen-induced arthritis (CIA), which was also confirmed by three-dimensional micro-computed tomography scan. TC-MTX markedly decreased the secretion of inflammatory cytokines both in the serum and in inflamed joints of CIA mice. Further, its therapeutic potential is comparable to that of etanercept, a biological agent that block tumor necrosis factor (TNF)-α. Importantly, the systemic cytotoxicity of TC-MTX was not detected. Thus, TC-MTX can be a new therapeutic modality for RA patients without systemic complications.

Original languageEnglish
Pages (from-to)1563-1572
Number of pages10
JournalBiomaterials
Volume33
Issue number5
DOIs
Publication statusPublished - 2012 Feb 1

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All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Lee, S. W., Kim, J. H., Park, M. C., Park, Y. B., Chae, W. J., Morio, T., Lee, D. H., Yang, S. H., Lee, S. K., Lee, S. K., & Lee, S. K. (2012). Alleviation of rheumatoid arthritis by cell-transducible methotrexate upon transcutaneous delivery. Biomaterials, 33(5), 1563-1572. https://doi.org/10.1016/j.biomaterials.2011.10.079