Topical Nano-Vesicular Spanlastics of Celecoxib: Enhanced Anti-Inflammatory Effect and Down-Regulation of TNF-α, NF-κB and COX-2 in Complete Freund's Adjuvant-Induced Arthritis Model in Rats

Background: Rheumatoid arthritis (RA) is an autoimmune disease that underlies chronic inflammation of the synovial membrane. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat RA. However, a long list of adverse events associated with long-term treatment regimens with NSAIDs negatively influences patient compliance and therapeutic outcomes. Aim: The aim of this work was to achieve site-specific delivery of celecoxib-loaded spanlastic nano-vesicle-based delivery system to the inflamed joints, avoiding systemic administration of large doses. Methodology: To develop spanlastic nanovesicles for transdermal delivery of celecoxib, modified injection method was adopted using Tween 80 or Brij as edge activators. Entrapment efficiency, vesicle size, ex vivo permeation, and morphology of the prepared nano-vesicles were characterized. Carbopol-based gels containing the selected formulations were prepared, and their clarity, pH, rheological performance, and ex vivo permeation were characterized. Celecoxib-loaded niosomes and noisome-containing gels were developed for comparison. The in vivo efficacy of the selected formulations was evaluated in a rat model of Freund's complete adjuvant-induced arthritis. Different inflammatory markers including TNF-alpha, NF-kappa B and COX-2 were assessed in paw tissue before and after treatment. Results: The size and entrapment efficiency of the selected spanlastic nano-vesicle formulation were 112.5 +/- 3.6 nm, and 83.6 +/- 2.3%, respectively. This formulation has shown the highest transdermal flux and permeability coefficient compared to the other investigated formulations. The spanlastics-containing gel of celecoxib has shown transdermal flux of 6.9 +/- 0.25 mu g/cm(2)/hr while the celecoxib niosomes-containing gel and unprocessed celecoxib-loaded gel have shown 5.2 +/- 0.12 mu g/cm(2)/hr and 0.64 +/- 0.09 mu g/cm(2)/hr, respectively. In the animal model of RA, the celecoxib-loaded spanlastics-containing gel significantly reduced edema circumference and significantly suppressed TNF-alpha, NF-kappa B and COX-2 levels compared to the niosomes-containing gel, the marketed diclofenac sodium gel, and unprocessed celecoxib-loaded gel. Conclusion: The spanlastic nano-vesicle-containing gel represents a more efficient site-specific treatment for topical treatment of chronic inflammation like RA, compared to commercial and other conventional alternatives.

Automated summary

The study aimed to develop a site-specific delivery system for Celecoxib using spanlastic nanovesicles or niosomes, to improve therapeutic outcomes while avoiding systemic administration of large doses. The developed spanlastic nano-vesicle formulation showed higher transdermal flux and permeability coefficient compared to other investigated formulations, effectively reducing inflammation markers in a rat model of arthritis.