Towards an arthritis flare-responsive drug delivery system

Local delivery of therapeutics for the treatment of inflammatory arthritis(IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritisactivity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassemblyand drug release controlled by the concentration of enzymes expressed during arthritisflares. In vitro, hydrogel loaded with triamcinolone acetonide(TA) releases drug on-demand upon exposure to enzymes or synovial fluidfrom patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent dye demonstrates flare-dependent disassemblymeasured as loss of fluorescence. Moreover, a single dose of TA-loaded hydrogel but not the equivalent doseof locally injected free TA reduces arthritisactivity in the injected paw. Together, our data suggest flare-responsive hydrogel as a promising next- generation drugdelivery approach for the treatment of IA.