Preparation, characterization and in-vivo evaluation of nanoemulsion based hydrogel of ferulic acid in imiquimod-induced psoriasis in rats

Psoriasis is skin inflammation caused by an immune system dysfunction, involving a complex interaction between immune cells and keratinocytes. The aim of this study was to develop nanoemulsion (NE) based hydrogel containing ferulic acid, a poorly water-soluble compound and evaluate its effect on imiquimod induced psoriasis like skin inflammation. Ferulic acid nanoemulsion (FA-NE) was prepared by ultra-sonication method. Castor oil, Tween-80 and propylene glycol were selected for NE preparation as oil phase surfactant and cosurfactant respectively based on solubility. The NE particle size (29.8 ± 0.49 nm) was within colloidal range, polydispersity index (0.21 ± 0.02) showed homogenous NE, zeta potential (28.5 ± 0.57 mV) indicated stable NE. Entrapment efficiency (96.26 ± 0.33%) and pH (6.8 ± 0.15) was also in suitable range. The rheological study results of FA-NE hydrogel indicated pseudoplastic behavior. The pH and spreadibility were 6.2 ± 0.15 and 8.2 ± 0.89 respectively, suitable for topical application. The optimized FA-NE hydrogel was tested on male Wistar rats (100-150 g) divided into five groups (n = 5). Psoriasis like disease was induced by applying 5% imiquimod (IMQ) cream for 7 days on the shaved dorsal skin of four groups (except normal group) and psoriasis area severity index (PASI) scoring were calculated. The application of optimized FA-NE hydrogel dramatically reduced TNF-α, IL-6, IL-17 A, IL-23, superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase biomarkers when compared to the disease group. These results were consistent with the in-silico docking studies with highest docking score observed with TNF-α. The treatment group's spleen index reduced significantly. Histopathological findings showed increased capillaries, skin thinning, small dermal projections, and inflammatory cells around blood vessels with 5% IMQ cream application and FA-NE hydrogel greatly reduced these psoriatic changes. Immunohistochemical Ki-67 analysis demonstrated that disease control rats expressed more protein than normal, treatment, and standard animals. The FA-NE hydrogel effectively reduced inflammation and oxidative stress in a rat model of psoriasis, suggesting its potential as a topical treatment.