Abstract

Naringenin (NR) is a plant-based flavonoid with poor aqueous solubility, which is indicated for the treatment of psoriasis due to its strong antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the non-steroidal NR-loaded nanocochleate hydrogel (NR-NC-G) for its skin permeation, safety, and efficacy in the treatment of psoriasis. First, nanoliposomes (NR-LIPO) were prepared and further chelated using calcium chloride to transform them into nanocochleates (NR-NCs). NR-NCs exhibited rolled sheet-like nanosized particles with a hydrodynamic diameter of approximately 160–170 nm, an encapsulation efficiency of 81–82%, and good colloidal stability, as indicated by a ζ-potential of −27 mV. To achieve a local reservoir-like action, nanocochleates were loaded into a hydrogel comprising of combination of Carbopol 934P and sodium alginate. NR-NC-G was characterised for its physical and rheological characteristics, and it exhibited uniform drug loading, long-term stability, and the ability to scavenge reactive oxygen species (ROS), as validated by various antioxidant assays. Furthermore, NR-NC-G reduced cellular ROS levels, nitrate accumulation, and mitochondrial healing ability in a lipopolysaccharide-stimulated RAW264.7 inflammation model, thereby proving its enhanced antioxidant and anti-inflammatory effects. The ex vivo skin permeation and dermatokinetic studies showed that NR-NC-G exhibited high permeation across the excised skin of BALB/C mice. The dermatokinetic studies showed that topical application of NR-NC-G provided 3.43 and 3.34-fold greater Cmax and AUC0−t in the epidermal layer, respectively, compared to the bulk NR solution. Overall, this novel nanoformulation enhances ROS scavenging capacity, improves cellular uptake, enhances skin permeation and retention, and suggests potential applications for treating psoriasis.