Blended ƙ-carrageenan and xanthan gum hydrogel containing ketoprofen-loaded nanoemulsions: Design, characterization, and evaluation in an animal model of rheumatoid arthritis.

This study reports the preparation of hydrogels (HG) made with xanthan gum (XG) and ƙ-carrageenan (KC) polysaccharides containing ketoprofen (KET)-loaded nanoemulsions (NK) and their evaluation in a rheumatoid arthritis (RA) model. The nano-based HGs exhibited nanometric-sized droplets (~ 100 nm), an acidic pH (5.10-6.83), drug content above 85%, a suitable spreadability factor, and pseudoplastic flow behavior. The most promising blend (HGCX 2:1) demonstrated sustained KET release, reaching 81.44 ± 6.11% after 5 h, and superior drug concentration in the skin layers (237.91 ± 41.0 µg/g). The formulation was selected due to its enhanced bioadhesiveness, with the HG-NK formulation showing the highest bioadhesion force and occlusion factor. RA was induced by complete Freund's adjuvant (CFA) intraplantar injection into the left hind paw of male and female Swiss mice. Treatments with HGs were applied to the animals' dorsal region for 7 days. Notably, HG-NK demonstrated remarkable efficacy, reversing mechanical sensitivity in male mice and significantly reducing thermal sensitivity in both genders. Moreover, HG-NK provided a significant reduction in paw edema (52-fold in males, 27-fold in females) and inflammatory markers, such as myeloperoxidase activity (32-fold in males, 14-fold in females) and lipid peroxidation (2.5-fold in males, twofold in females). The formulation also promoted greater permeation of KET across the skin. These findings underscore the significant reduction in inflammatory markers by the HG-NK formulation, highlighting its potent anti-inflammatory effects and potential as a promising therapeutic strategy for managing RA.