Application of Box-Behnken design for the optimization of Khellin-loaded ethosomes formulation for the management of psoriasis in mice

The objective of the present study was to develop and optimize Khellin-loaded ethosomes formulation to enhance the topical delivery of Khellin for the management of psoriasis. Based on vesicle size, polydispersity (PdI) and encapsulation efficiency, the formulation was optimized using the "3-factor 3-level", Box-Behnken design (BBD). Antioxidant, Anti-inflammatory and Anti-psoriatic activity were further assessed for the optimized formulation. The optimized formulation carried vesicles with a size of 214.64 +/- 0.04 nm, PdI 0.387 +/- 0.001 and an encapsulation efficiency of 68.38 +/- 0.01%. Rhodamine-B loaded formulation was applied to mice skin, and the penetration depth was measured using confocal laser scanning microscopy (CLSM). It was found that the Rhodamine-B solution penetrated mice's skin to a depth of 20.0 mu m. However, the Rhodamine-B loaded ethosomes formulation penetrated mice's skin to a depth of 55.0 mu m. Further, the Khellin-loaded ethosomes formulation possessed strong antioxidant activity, presented a good reduction in paw edema, and showed good anti-inflammatory activity. In addition, the prepared Khellin-loaded ethosomes formulation exhibited considerable effects against psoriasis.