Dexamethasone-Loaded Thermosensitive Hydrogel Suppresses Inflammation and Pain in Collagen-Induced Arthritis Rats

• Published in: Drug design, development and therapy Vol. 14; pp. 4101 - 4113
• Main Authors: Wang, Qi-Shan, Xu, Bing-Xin, Fan, Kai-Jian, Li, Yun-Wu, Wu, Jing, Wang, Ting-Yu
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2020; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Animal models; Animals; anti-inflammatory; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - pathology; Arthritis, Experimental - psychology; Body weight; Body Weight - drug effects; Borax; Central nervous system depressants; Chitosan; Collagen; Controlled release; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - pharmacology; Dinoprostone - metabolism; dlth; Dorsal root ganglia; Drug withdrawal; Edema; Edema - drug therapy; Experiments; Ganglia; Ganglia, Spinal - drug effects; Glycerol; Health aspects; Hydrogels; Hyperplasia; Immunization; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Injection; Interleukin-17 - metabolism; Joints (anatomy); Laboratory animals; Male; Nerve growth factor; NF-kappa B - drug effects; NF-kappa B - metabolism; NF-κB protein; Original Research; Pain; Pain - chemically induced; Pain - drug therapy; Pain management; Pain Threshold - drug effects; pain-relieving; Plantar pressure; Polymerase chain reaction; Prostacyclin; Prostaglandin D2; Prostaglandin D2 - metabolism; Prostaglandin E2; Prostaglandins E; Rats; Rats, Wistar; Remission; Rheumatoid arthritis; Rheumatoid factor; Rodents; Steroids; Sustained release; Swelling; Synovial Membrane - pathology; Synovium; Transcription; Variance analysis; Western blotting; China; anti-inflammatory; dexamethasone-loaded thermosensitive hydrogel; DLTH; rheumatoid arthritis; RA; pain-relieving
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S256850

To overcome negative adverse effects and improve therapeutic index of dexamethasone (Dex) in rheumatoid arthritis (RA), we developed a novel sustained release formulation-intra-articular injectable dexamethasone-loaded thermosensitive hydrogel (DLTH) with chitosan-glycerin-borax as carrier for the remission of inflammation and pain. The focus of this article is to explore both anti-inflammatory and pain-relieving effects of DLTH joint injection in bovine type-II collagen-induced arthritis (CIA) rats. Wistar rats were randomized into three groups, including the normal group (n=6), the model group (n=6) and the DLTH group (n=10). Joint injection of DLTH (1mg/kg Dex per rat) was injected on day 12 in the DLTH group twice a week for three weeks. Clinical signs of body weight, paw swelling and arthritis scores, histologic analysis, hind paw mechanical withdrawal threshold (MWT), plantar pressure pain threshold (PPT) were taken into consideration. Serum contents of IL-17A, prostaglandin E2 (PGE2), prostacyclin 2 (PGI2) and prostaglandin D2 (PGD2), real-time polymerase chain reaction (PCR) analysis of inflammatory factors and pain-related mediators in synovium and dorsal root ganglia (DRG), Western blotting of NF-κB in synovium were all evaluated. Paw swelling, arthritis scores and joint inflammation destruction were all attenuated in the DLTH-treated group. Results showed that DLTH not only down-regulated serum IL-17A, but also mRNA levels of inflammatory factors and NGF, and key proteins contents of the NF-κB pathway in synovium. Increases of MWT and PPT in DLTH-treated rats elucidated pain-reducing effects of DLTH. Elevated serum PGD2 levels and declines of serum PGE2 and PGI2, and inflammatory and pain-related genes in DRGs in the DLTH group were also recorded. These data elucidated that DLTH joint injection impeded synovial inflammation processes through down-regulating transcription activity of NF-κB pathway, and intra-articular DLTH may aid in the regulation of RA pain through regulating inflammation and pain conduction process.