Hyaluronic/Poloxamers-co-decorated nanoemulsion containing naringenin and quercetin for psoriasis treatment

Psoriasis is a chronic autoimmune disorder characterized by persistent inflammation that progressively impairs the quality of life. Conventional corticosteroids suppress inflammatory mediators but fail to inhibit immune cell activation, leading to chronicity and long-term adverse effects. Quercetin and naringenin exhibit potent and synergistic antioxidant and anti-inflammatory properties, but their efficacy is hindered by low solubility and permeability. This study developed a quercetin-naringenin nanoemulsion hydrogel patch (NE-QNH) decorated with a hyaluronate-phospholipid complex (HA-PC) and modified with thermoresponsive polymers for targeted and controlled delivery. The nanoemulsion was optimized using a 2² factorial design based on critical quality attributes, including droplet size, polydispersity index, zeta potential, and encapsulation efficiency (EE). Hydrogel patches with varying polymer were evaluated for viscosity, drying time, spreadability, and elasticity. Ex-vivo permeation studies were conducted using porcine skin, and in-vivo efficacy was confirmed in a psoriasis model to validate the therapeutic outcome. The optimized NE-QNH exhibited a particle size of 14.94 ± 0.06 nm, a zeta potential of -9.78 ± 0.20 mV, an effective EE exceeding 80%, and high stability. The HA-PC complex decorated 87% of the nanoemulsion surface, while polymer modification formed an external matrix. Ex-vivo and in-vivo studies demonstrated a 240% increase in permeation and a 290% improvement in retention, epidermal recovery, and a significant reduction in psoriasis area and severity index, indicating that NE-QNH is a promising strategy for psoriasis therapy.