Towards an arthritis flare-responsive drug delivery system

• Published in: Nature communications Vol. 9; no. 1; pp. 1275 - 11
• Main Authors: Joshi, Nitin, Yan, Jing, Levy, Seth, Bhagchandani, Sachin, Slaughter, Kai V., Sherman, Nicholas E., Amirault, Julian, Wang, Yufeng, Riegel, Logan, He, Xueyin, Rui, Tan Shi, Valic, Michael, Vemula, Praveen K., Miranda, Oscar R., Levy, Oren, Gravallese, Ellen M., Aliprantis, Antonios O., Ermann, Joerg, Karp, Jeffrey M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.04.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 59; 59/5; 639/166/985; 639/301/54/152; 692/4023/1670/498; Animals; Anti-Inflammatory Agents - administration & dosage; Arthritis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Biocompatible Materials - chemistry; Chondrocytes - cytology; Dismantling; Drug delivery; Drug Delivery Systems; Drug dosages; Drug Liberation; Enzymes; Fluorescence; Fluorescent dyes; Fluorescent indicators; Humanities and Social Sciences; Humans; Hydrogels; Hydrogels - chemistry; Inflammation; Inflammation - drug therapy; Male; Mice; Mice, Inbred C57BL; Monocytes - cytology; multidisciplinary; Rheumatoid arthritis; Science; Science (multidisciplinary); Symptom Flare Up; Synovial Fluid; Synoviocytes - cytology; Triamcinolone acetonide; Triamcinolone Acetonide - administration & dosage
• ISSN: 2041-1723; 2041-1723
• 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. The treatment of inflammatory arthritis by local delivery of therapeutics is limited by short half-lives of drugs. Here the authors demonstrate a hydrogel platform that titrates drug release to arthritis activity.