Abstract
Purpose: This study aimed to enhance the therapeutic effect of fluticasone (FP) for psoriasis using black cumin oil-based nanostructured lipid carriers (NLCs) with dual deposition/permeation capabilities to achieve high drug localization within the viable skin layers (deposition) for targeted topical action, while concurrently facilitating efficient drug flux through the skin (permeation) to address the full depth of psoriatic plaques. Methods: Oil selection followed a preliminary NLC optimization study. Characterization used microscopy, FTIR, DSC, ex vivo skin permeation and deposition, and in vivo pharmacodynamics with imiquimod-induced psoriatic mice. Results: The optimized NLC showed a size of 171.3 nm, a PDI of 0.37, and a zeta potential of -32.3 mV. Ex-vivo data showed dual local/systemic distribution, with FP deposition in the stratum corneum and epidermis, plus superior permeation versus marketed cream. An in vivo study revealed PASI score improvement up to 77%. IL-6 and IL-1α levels were significantly reduced. Histology showed inflammation decline. Conclusion: Results demonstrated improved anti-psoriatic action using the dual distribution/combinatorial approach with the optimized formulation. The data confirmed that the black cumin oil-based NLC formulation offers better outcomes than the standard cream by enhancing FP skin targeting, penetration, and anti-inflammatory response in psoriatic models.