Fiehn C et al. – Targeted drug delivery by in vivo coupling of a prodrug of methotrexate (MTX) to endogenous albumin is superior to MTX in the treatment of collagen-induced arthritis (CIA). Methods
Study to examine the effect of an albumin-binding prodrug of MTX in the treatment of murine CIA
The prodrug AWO54 with the formula EMC-D-Ala-Phe-Lys-Lys-MTX binds selectively to the cysteine-34 position of endogenous albumin
This prodrug acts as a macromolecular drug carrier for MTX to the site of inflammation
The CIA model was used to evaluate the anti-arthritic effect of the compound after intravenous application
Results
The albumin-bound form of AWO54 was efficiently cleaved and released a MTX lysine derivative
AWO54 suppressed collagen-induced arthritis in a dose-dependent manner and was superior to MTX
To obtain a similar effect only about 20% of the MTX-equivalent dose of AWO54 had to be given vs MTX
The efficacy of the drug was tested in two different stages of CIA
While both, MTX and AWO54 inhibited arthritis in an early stage of the disease, in a later stage only AWO54 showed inhibitory effect vs control
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