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- W2022838078 abstract "We previously reported that a conjugate of hyaluronic acid (HA) and methotrexate (MTX) could be a prototype for future osteoarthritis drugs having the efficacy of the two clinically validated agents but with a reduced risk of the systemic side effects of MTX by using HA as the drug delivery carrier. To identify a clinical candidate, we attempted optimization of a lead, conjugate 1. Initially, in fragmentation experiments with cathepsins, we optimized the peptide part of HA–MTX conjugates to be simpler and more susceptible to enzymatic cleavage. Then we optimized the peptide, the linker, the molecular weight, and the binding ratio of the MTX of the conjugates to inhibit proliferation of human fibroblast-like synoviocytes in vitro and knee swelling in rat antigen-induced monoarthritis in vivo. Consequently, we found conjugate 30 (DK226) to be a candidate drug for the treatment of osteoarthritis." @default.
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- W2022838078 date "2010-02-01" @default.
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- W2022838078 title "Synthesis and optimization of hyaluronic acid–methotrexate conjugates to maximize benefit in the treatment of osteoarthritis" @default.
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- W2022838078 doi "https://doi.org/10.1016/j.bmc.2009.12.053" @default.
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