Development and preclinical assessment of nanoemulgel loaded with phytoconstituents for the management of rheumatoid arthritis

In recent years, natural ingredients have gained importance for therapeutic treatment due to their minimal toxicity. However, the delivery of these phytoconstituents poses a challenge to provide better efficacy. Current research reports the development of nanoemulgel (NEG) loaded with ginger oleoresin (GOR) and lipid guggul extract (LGE) for the management of rheumatoid arthritis (RA). The nanoemulsion (NE) was developed using the spontaneous emulsification technique by the pseudo-ternary method. The optimized nanoemulsion exhibited globule size of 16.08 +/- 2.55 nm, PDI of 0.187 +/- 0.06, and zeta potential of -22.4 +/- 0.31 mV. The cumulative release from in vitro diffusion studies at pH 7.4 was about 99.72 +/- 3.47%, 57.98 +/- 2.11%, and 86.42 +/- 5.13% of 6-gingerol, E-guggulsterone, and Z-guggulsterone respectively at the end of 24 h. The ex vivo studies on porcine ear skin showed sustained release with 92.8 +/- 3.21% for 6-gingerol, 55.61 +/- 0.91% for E-guggulsterone, and 84.2 +/- 4.22% for Z-guggulsterone released at the end of 24 h. The cell culture studies on RAW 264.7 cells indicated a robust inhibition of LPS-induced IL-6 and TNF-alpha production indicating its efficacy in the management of RA. The preclinical studies on male Wistar rats suggest that the developed NEG exhibited a comparable decrease in paw edema inflammation as compared to the marketed diclofenac sodium gel. These encouraging results demonstrate the potential of the developed nanoemulgel containing combination of GOR and LGE for the management of RA.