%0 Journal Article %J Nat Commun %D 2018 %T Towards an arthritis flare-responsive drug delivery system. %A Joshi, Nitin %A Yan, Jing %A Levy, Seth %A Bhagchandani, Sachin %A Slaughter, Kai V %A Sherman, Nicholas E %A Amirault, Julian %A Wang, Yufeng %A Riegel, Logan %A He, Xueyin %A Rui, Tan Shi %A Valic, Michael %A Vemula, Praveen K %A Miranda, Oscar R %A Levy, Oren %A Gravallese, Ellen M %A Aliprantis, Antonios O %A Ermann, Joerg %A Karp, Jeffrey M %X

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 arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares. In vitro, hydrogel loaded with triamcinolone acetonide (TA) releases drug on-demand upon exposure to enzymes or synovial fluid from patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent dye demonstrates flare-dependent disassembly measured as loss of fluorescence. Moreover, a single dose of TA-loaded hydrogel but not the equivalent dose of locally injected free TA reduces arthritis activity in the injected paw. Together, our data suggest flare-responsive hydrogel as a promising next-generation drug delivery approach for the treatment of IA.

%B Nat Commun %V 9 %P 1275 %8 2018 Apr 03 %G eng %N 1 %R 10.1038/s41467-018-03691-1