Towards an arthritis flare-responsive drug delivery system

Nat Commun. 2018 Apr 3;9(1):1275. doi: 10.1038/s41467-018-03691-1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Biocompatible Materials / chemistry
  • Chondrocytes / cytology
  • Drug Delivery Systems*
  • Drug Liberation
  • Humans
  • Hydrogels / chemistry
  • Inflammation / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / cytology
  • Symptom Flare Up
  • Synovial Fluid
  • Synoviocytes / cytology
  • Triamcinolone Acetonide / administration & dosage


  • Anti-Inflammatory Agents
  • Biocompatible Materials
  • Hydrogels
  • Triamcinolone Acetonide