A Box-Behnken-Optimized Phytosomal Strategy for Diosgenin: Enhancing Oral Delivery and Antipsoriatic Efficacy in a Preclinical Model.

Psoriasis is a chronic inflammatory skin disorder characterized by excessive keratinocyte proliferation and immune dysregulation, affecting patients' quality of life. Diosgenin (DG) is a natural steroidal sapogenin with potent anti-inflammatory and immunomodulatory effects. These effects could help treat psoriatic symptoms; however, poor solubility and limited dissolution limit its therapeutic potential. The current study aimed to develop diosgenin-loaded phytosomes (DG-PS) using the Box-Behnken design and to evaluate their physicochemical characteristics and antipsoriatic efficacy. The DG-PS were prepared using the thin-film hydration technique. The DG-PS were optimized with respect to phosphatidylcholine concentration, temperature, and evaporator rotation speed. The optimal formulation of DG-PS-15 showed a particle size of 201.1 nm, a polydispersity index of 0.4027, and a zeta potential of -36.87 mV. Characterization of DG-PS-15 by differential scanning calorimetry, Fourier-transform infrared, and X-ray diffraction demonstrated successful complexation with phospholipids, enhanced amorphous characteristics, and stable molecular interactions. Meanwhile, DG-PS-15 exhibited higher solubility, sustained in vitro drug release, and an entrapment efficiency of 68.55%. In vivo activity testing in an imiquimod-induced psoriatic mouse model revealed that DG-PS-15 at a 50 mg/kg dose significantly reduced erythema, scaling, and skin thickness. Histopathological and biochemical analyses further supported the enhanced antipsoriatic efficacy and antioxidant activity of DG following phytosomal complexation. These findings suggest that phytosomal complexation may be a valuable strategy to enhance the therapeutic efficacy of DG, thereby improving treatment outcomes and patient well-being.