Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis.

摘要: A novel linear multifunctional polyethylene glycol (PEG)-dexamethasone (Dex) conjugate (click PEG-Dex) was synthesized using facile Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a click reaction). Dex conjugated to the PEG via an acid-labile hydrazone bond allow drug release in a pathophysiological environment. To evaluate PEG’s potential as versatile delivery platform, PEG-Dex conjugates were tested adjuvant-induced arthritis (AA) rat model. In vivo optical imaging data confirmed arthrotropism of arthritic rats. long-term treatment study revealed that single administration provided sustained (>15 days) amelioration ankle joint inflammation AA Treatment with equivalent dose dexamethasone phosphate sodium (free Dex) only temporal resolution arthritis, which recurred upon withdrawal. Further histological and bone mineral density comparison between ankle...