Network pharmacology guided development and optimization of curcumin and sesame oil nanostructured lipid carriers for psoriasis

Psoriasis is a chronic inflammatory skin disease that requires long-term management. Natural compounds such as curcumin and sesame oil have shown promising antioxidant and anti-inflammatory properties; in contrast, their practical application is hampered by poor solubility, low stability, and limited skin permeability. This study aimed to design, optimize, and characterize a nanostructured lipid carrier (NLC) co-loaded with curcumin and sesame oil for potential dermal application in psoriasis, integrating a network pharmacology approach to validate therapeutic relevance. The NLC formulation was optimized using a response surface methodology (RSM) approach with two independent variables liquid-to-solid lipid ratio (0.25-0.40) and homogenization time (5-10 min) to minimize particle size (PS) and polydispersity index (PDI). The optimized formulation achieved a PS of approximately 132.420 nm, PDI of 0.208, and a desirability score of 0.903. Physicochemical characterizations including DLS, SEM, and XRD confirmed the nanoscale, spherical, and amorphous nature of the particles. In vitro release studies demonstrated a sustained release profile of curcumin over 24 h. MTT assay on human fibroblasts indicated good biocompatibility, while DPPH assay confirmed strong antioxidant activity comparable to free curcumin and sesame oil. The co-loaded curcumin-sesame oil NLC demonstrated desirable physicochemical properties, providing a promising platform for future preclinical investigations in inflammatory skin disorders such as psoriasis. Network pharmacology analysis identified 74 overlapping targets of curcumin, sesame oil, and psoriasis, with key hub genes (e.g., TNF, IL1B, IL10, CASP3) involved in inflammation, oxidative stress, and apoptosis. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment revealed modulation of IL-17, TNF, and oxidative stress pathways, underscoring the multi-target therapeutic potential of curcumin and sesame oil in psoriasis. Collectively, this study establishes a dual-evidence strategy combining in silico validation and formulation science to support the translational development of curcumin and sesame oil-based nanotherapeutics for inflammatory skin diseases like psoriasis.