The Design and Development of a Dexamethasone‐Tranfersome‐PF‐127/HA Stimuli‐Responsive Hydrogel for Intra‐Articular Therapy in Osteoarthritis

Osteoarthritis (OA), a prevalent degenerative joint disease, significantly impairs mobility and quality of life, often necessitating frequent intra‐articular (IA) injections to manage pain and inflammation. This study develops and characterizes a dexamethasone (DEX)‐loaded transfersome‐based hydrogel (DEX‐tNPs‐PF127/HA) for IA delivery in OA treatment. The formulation is optimized to enable controlled drug release and improved stability, aiming to reduce IA injection frequency while maintaining therapeutic efficacy. DEX‐loaded transfersomes (tNPs) are synthesized via thin‐film hydration and incorporated into a thermoresponsive hydrogel composed of Pluronic F‐127 (PF‐127) and hyaluronic acid (HA). Morphological evaluation, particle size analysis, zeta potential measurements, encapsulation efficiency assessment, and rheological characterizations are conducted. DEX‐tNPs exhibit a nanoscale size (∼76 nm), with a high encapsulation efficiency (98%) and a cationic surface charge. In vitro drug release studies demonstrate sustained DEX release over 6 weeks under physiological conditions. Biocompatibility, determined using RAW 264.7 macrophages, reveals cell viability above 70%. Interleuken‐4 (IL‐4) quantification indicates an initial immunomodulatory effect from the blank‐tNPs hydrogel, with a slight reduction upon DEX encapsulation. The hydrogel exhibits favorable shear‐thinning and self‐healing properties, facilitating smooth IA injection. These findings highlight the DEX‐tNPs‐PF127/HA hydrogel as a promising candidate for sustained IA therapy in OA. Further in vivo studies are warranted.