A novel dexamethasone-loaded liposome alleviates rheumatoid arthritis in rats

Mediators of Inflammation

Fan

et al. 2020

To investigate the crosstalk between cartilage and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), we adopted an in vitro coculture system model of collagen-induced arthritis (CIA) cartilage and CIA FLS monolayer. CIA rat samples of the synovium and femur head were collected for isolation of FLS and coculture system. Cartilages were treated with vehicle (Ctrl group), 10 ng/mL interleukin- (IL-) 1α (IL-1α group), and 10 ng/mL IL-1α plus 10 μM dexamethasone (Dex group) for 3 days before coculture with FLS for further 2 days. After the coculture, FLS were collected to determine the influences of articular cartilage on synoviocytes. Whether the CypB-CD147 signaling pathway is involved in the interactions between cartilage and FLS is assayed. Results showed that IL-1α-stimulated CIA cartilage promoted the proliferation and reduced the apoptosis of FLS. Increased inflammatory cytokines and decreased p57 expression were found in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. Upregulation of NF-κB and I-κB kinase β (IKK-β) and downregulation of the inhibitor of NF-κBα (I-κBα) protein were observed in cocultured FLS. After coculture, significant increases in the expression of cyclophilin B (CypB) and CD147 were observed in CIA cartilage and FLS, respectively. Furthermore, results of immunofluorescence staining showed that the anti-CD147 antibody significantly suppressed p65 nuclear translocation in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. In conclusion, inflammatory effects in the cartilage-FLS coculture system are associated with the CypB-CD147 mediating NF-κB pathway which may further enhance the inflammation in RA.

Section: Discussionmentioning

confidence: 99%

CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis

Mediators of Inflammation

Fan

et al. 2020

“…[40] Additionally, Jia et al prepared Dex-loaded liposomes with an average diameter of 58 nm and showed that, compared with free Dex, Dex-loaded liposomes generated a greater level of reduction in paw swelling and substantially decreased the serum levels of proinflammatory cytokines, including TNF-and IL-1 , in arthritic rats. [41] Ulmansky et al reported a sterically stabilized PEGylated liposome loaded with two glucocorticoid (GC) prodrugs, and showed similar therapeutic efficacies for these PEGylated liposomes when they were given via either i.v. or s.c. injection.…”

Section: Liposomesmentioning

confidence: 99%

Nanomedicine Strategies for Anti‐Inflammatory Treatment of Noninfectious Arthritis

Chen

Adv Healthcare Materials

Lee

et al. 2021

Noninfectious arthritis (NIA) comprises a class of chronic and progressive inflammatory disorders that require early-stage management to prevent disease progression. The most common forms include osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gouty arthritis. Current treatments involve nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs and glucocorticoids to alleviate clinical symptoms, although regular use of these can result in a high risk of chronic kidney disease and heart failure, as well as severe adverse gastrointestinal effects. Nanomedicine offers unique opportunities to address these challenges and improve therapeutic efficacy due to its ability to deliver therapeutics locally in a sustained manner, thus extending the half-life, improving bioavailability, and reducing the side effects of these agents. This review includes a comprehensive analysis of the mechanisms of various treatment options for NIA and highlights recent progress and emerging strategies in treating NIA with nanomedicine platforms, particularly related to long-term biosafety and nonspecific targeting in designing nanomedicine delivery systems.

“…The study revealed that certain fullerene reduced TNF‐α‐induced mediator release from mast cells 98. Jia et al developed an inflammation‐targeted delivery system based on a liposomal carrier‐loaded Dex against arthritis 51. Meanwhile, Zhang et al used CC and FA to fabricate PSA micelles for the targeted delivery of Dex, resulting in the suppression of TNF‐α and IL‐6 expression 67…”

Section: Nanotherapeutics Of Ra Based On Nanodrugsmentioning

confidence: 99%

Recent Advances in Nanotheranostics for Treat‐to‐Target of Rheumatoid Arthritis

Adv Healthcare Materials

Meng

et al. 2020

Early diagnosis, standardized treatment, and regular monitoring are the clinical treatment principle of rheumatoid arthritis (RA). The overarching principles and recommendations of treat‐to‐target (T2T) in RA advocate remission as the optimum aim, especially for patients with very early disease who are initiating therapy with anti‐RA medications. However, traditional anti‐RA drugs cannot selectively target the inflammatory areas and may cause serious side effects due to its short biological half‐life and poor bioavailability. These limitations have significantly driven the research and application of nanomaterial‐based drugs in theranostics of RA. Nanomedicines have appropriate sizes and easily modified surfaces which can enhance their biological compatibility and prolong circulation time of drug‐loading systems in vivo. Traditional T2T regimens cannot evaluate the efficacy of drugs in real time, while clinical drug nanosizing can realize the integration of diagnosis and treatment of RA. This review bridges clinically proposed T2T concepts and nanomedicine in an integrated system for RA early‐stage diagnosis and treatment. The most advanced progress in various nanodrug delivery systems for theranostics of RA is summarized, establishing a clear path and a new perspective for further optimization of T2T. Finally, the key facing challenges are discussed and prospects are addressed.