| Literature DB >> 29615615 |
Nitin Joshi1,2,3, Jing Yan3,4, Seth Levy3,4, Sachin Bhagchandani1, Kai V Slaughter1, Nicholas E Sherman1, Julian Amirault1, Yufeng Wang1, Logan Riegel1, Xueyin He1, Tan Shi Rui1, Michael Valic1, Praveen K Vemula1,2,3,5, Oscar R Miranda1,2,3, Oren Levy1,2,3, Ellen M Gravallese6, Antonios O Aliprantis3,4,7, Joerg Ermann8,9, Jeffrey M Karp10,11,12.
Abstract
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.Entities:
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Year: 2018 PMID： 29615615 PMCID： PMC5882944 DOI： 10.1038/s41467-018-03691-1
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919