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Purpose: To investigate the in vitro anti-skin-aging properties of Cratoxylum formosumextract and encapsulate this plant extract in nanostructured lipid carriers (CFE-NLCs) fordermal application.Methods: The biological properties of the plant extract, including enhanced procollagen typeI synthesis and anti-matrix metalloproteinase activity, were evaluated to assess its cosmeticbenefits. An artificial neural network (ANN) coupled with K-fold cross-validation was appliedto investigate the effects of the formulants and optimize the CFE-NLCs. The physicochemicalproperties, percutaneous absorption, and irritation potential of the CFE-NLCs were analyzed.Results: Liquid chromatography-mass spectrometry analysis revealed that CFE contained5-O-caffeoylquinic acid as the vital constituent. Appropriate skin-care properties were alsodemonstrated with respect to enhanced type I procollagen synthesis and the inhibition of MMP-1, MMP-3, and MMP-9 in primary human dermal fibroblasts. The optimal CFE-NLCs exhibitedbetter skin absorption and biocompatibility and lower irritation potential than the free botanicalextract solution.Conclusion: The findings obtained highlight CFE-NLCs as promising skin-care ingredients.