Design and development of piperine-loaded polymeric micellar gel for the management of rheumatoid arthritis

This study aims to develop a piperine-loaded polymeric micellar gel that overcomes piperine's poor aqueous solubility and limited partitioning into deeper viable skin/tissue layers, thereby improving its permeation, sustained release, and deep tissue availability for the management of rheumatoid arthritis. Polymeric micelles were prepared by the solvent evaporation method. A 2³ full factorial design (Minitab) was used to evaluate the effects of the drug:polymer ratio, surfactant type, and surfactant concentration on particle size and entrapment efficiency. The optimized gel was characterized by in vitro drug release, ex vivo skin permeation, and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay. Anti-arthritic efficacy was evaluated in Complete Freund's Adjuvant-induced arthritic Wistar rats. The optimized formulation containing 1% Poloxamer 188, a 1:25 drug:Soluplus® ratio, and 2.5% PVA exhibited a particle size of 70.19 nm and 95.38% entrapment efficiency. The formulation showed sustained drug release (91 ± 2.4% over 24 h) compared with the conventional gel (73.2% over 24 h). Ex vivo studies demonstrated 91.38% drug permeation with a flux of 1.6241 µg/cm²/h and a permeation coefficient of 0.518 cm/h. In vivo evaluation showed significant reductions in paw edema and WBC count, with restoration of RBC and hemoglobin levels. Piperine-loaded polymeric micellar gel demonstrated sustained release, enhanced skin permeation, and promising anti-arthritic activity in a preclinical model. However, these findings are limited to a single 21-day animal study, and further mechanistic and clinical studies are required to confirm its therapeutic potential in humans.