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Response surface plots illustrating the effect of surfactant (X1), oil phase (X2) and aqueous phase containing 40% cosurfactant (X3) on the drug deposition in skin of naringenin-loaded submicron emulsion formulations.Submicron emulsion system is one kind of submicron-carrier that can ensure close contact and increase the amount of drug transport into the skin. In the present study, naringenin was loaded into a submicron emulsion system for topical applications. The enhancement effect of drug permeability through skin, stability, and skin irritation of naringenin-loaded submicron emulsions were evaluated. The results showed that the transdermal amount and deposition amount in skin of naringenin from submicron emulsion formulations were significantly increased when compared to the control group of saturated aqueous solution of naringenin. The drug-loaded submicron emulsions showed thermodynamic stability after centrifugation and cooling–heating cycle tests. The level of drug was more than 98% after 3 months of storage at 25 °C and 40 °C. In skin irritation test, the result also demonstrated that naringenin-loaded submicron emulsion had less skin irritation, indicating that the formulation can possibly be developed for topical application.