Towards an arthritis flare-responsive drug delivery system.
|Towards an arthritis flare-responsive drug delivery system.
|Year of Publication
|Joshi N, Yan J, Levy S, Bhagchandani S, Slaughter KV, Sherman NE, Amirault J, Wang Y, Riegel L, He X, Rui TShi, Valic M, Vemula PK, Miranda OR, Levy O, Gravallese EM, Aliprantis AO, Ermann J, Karp JM
|2018 Apr 03
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.
|PubMed Central ID
|R03 AR066357 / AR / NIAMS NIH HHS / United States
R56 AR063866 / AR / NIAMS NIH HHS / United States