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

 Sang-Won Leea  ;  Ji-Hye Kima  ;  Min-Chan Parka  ;  Yong-Beom Parka  ;  Wook Jin Chaeb  ;  Tomohiro Morioc  ;  Dong-Ho Leed  ;  Sang-Hwa Yange  ;  Seung-Kyou Leed  ;  Soo-Kon Leea 
 BIOMATERIALS, Vol.33(5) : 1563-1572, 2012 
Journal Title
Issue Date
Administration, Cutaneous ; Animals ; Arthritis, Experimental/drug therapy ; Arthritis, Experimental/pathology ; Arthritis, Rheumatoid/diagnostic imaging ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Rheumatoid/pathology ; Cell Death/drug effects ; Cell Membrane Permeability/drug effects* ; Cytokines/metabolism ; Dose-Response Relationship, Drug ; Drug Delivery Systems/methods* ; Etanercept ; Immunoglobulin G/pharmacology ; Immunoglobulin G/therapeutic use ; Inflammation Mediators/metabolism ; Kinetics ; Male ; Methotrexate/administration & dosage ; Methotrexate/chemistry ; Methotrexate/pharmacology* ; Methotrexate/therapeutic use* ; Mice ; Receptors, Tumor Necrosis Factor/therapeutic use ; Tetrahydrofolate Dehydrogenase/metabolism ; Tissue Distribution/drug effects ; Treatment Outcome ; X-Ray Microtomography
Arthritis ; Drug delivery ; Inflammation ; Immunomodulation ; Cytotoxicity
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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Ji Hye(김지혜)
Park, Min Chan(박민찬) ORCID logo https://orcid.org/0000-0003-1189-7637
Park, Yong Beom(박용범)
Lee, Sang Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
Lee, Soo Kon(이수곤)
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