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In this study, VE-loaded nanostructured lipid carriers (VE-NLC) were produced by melt high pressure homogenization, consisting of biocompatible materials. The optimal production parameters of VE-NLC dispersion were investigated to obtain small particle size and narrow size distributions of VE-NLC for its application in topic administration and cosmetic field. TEM micrograph showed that VE-NLCs were all irregular spherical particles with a narrow size distribution. Physically stable VE-NLC with a narrow size distribution in the nanometer range and up to 40% lipid content was successfully produced. Cytotoxicity, cellular activity and photoprotection of VE-NLC dispersions to HaCaT keratinocytes were measured by MTT assay. Cell experiment results showed that no cytotoxicity was observed when VE-NLC dispersion with 5% lipid concentration was diluted by 600-fold. Further, cellular uptake and penetration of VE were necessary for its protection against photodamages of HaCaT keratinocytes induced by UVB irradiation. This work suggests that incorporation of VE in nanostructured lipid carriers confers photoprotection against UVB-induced photodamages.