Psoriasis is a chronic, autoimmune-driven inflammatory skin disorder characterized by erythematous, scaly lesions, excessive keratinocyte proliferation, and infiltration of inflammatory cells. Conventional therapies, such as corticosteroids, are often associated with limitations including adverse effects, inadequate skin penetration, and poor patient compliance. These challenges highlight the need for more effective and safer topical drug delivery systems.

Resveratrol (RSV), a plant-derived polyphenol obtained from Vitis vinifera L., has demonstrated significant anti-inflammatory and antioxidant potential for the treatment of psoriasis. However, its clinical application is limited due to poor aqueous solubility, instability, and restricted skin permeability.

To overcome these limitations, resveratrol-loaded dual-carrier conjugated nanoparticles (RSVNPL) were developed using biocompatible soya lecithin and poly(lactic-co-glycolic acid) (PLGA). These nanoparticles were further incorporated into a Carbomer 974P-based hydrogel to form a nanocomposite hydrogel (RSVNPGel), designed to enhance ease of application and prolong skin residence time.

The developed formulation exhibited improved physicochemical properties, including enhanced spreadability, adhesiveness, and storage stability. Permeation studies demonstrated significantly higher accumulation of resveratrol in both the epidermis and dermis compared to conventional resveratrol gel formulations.

In an imiquimod-induced psoriatic mouse model, RSVNPGel showed significant therapeutic efficacy, including reduced epidermal thickness, decreased inflammatory cell infiltration, and suppression of key histopathological features. Psoriasis Area and Severity Index (PASI) scoring further confirmed a substantial improvement in disease severity compared to the control group.

Importantly, systemic safety was validated, as serum biochemical markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine remained within normal ranges. Histological examination of major organs also revealed no signs of toxicity.

Overall, RSVNPGel represents a promising, sustainable, plant-based nanocarrier system for the effective and safe topical management of psoriasis. It enhances the dermal delivery of resveratrol, minimizes systemic exposure, and aligns with green pharmaceutical design principles.