Experimental Design in Formulation Optimization of Vitamin K1 oxide-loaded Nanoliposomes for Skin Delivery

Abstract Due to the vitamin K1 sensitizing potential, the oxidized-isoform of vitamin K1 (vitamin K1 oxide, VKO), has been recently used for treating laser-induced purpura and hyperpigmentation in cosmetics. The objective of this study was to formulate VKO in nanoliposomes by using Box–Behnken experimental design to obtain an optimized formula with higher efficiency. The ratio of phospholipid to cholesterol (PC/CHO ratio), VKO concentration and sonication time in low, medium, and high levels were independent variables, while the percent of VKO entrapment efficiency (EE%) and vesicle size were selected as dependent variables. Optimum desirability was identified and an optimized formulation was prepared, characterized, and selected for in vitro VKO release and ex vivo skin permeation. The PC/CHO ratio showed the greatest effect on both responses (P