Amer, Reham IEzzat, Shahira MAborehab, Nora MRagab, Mai FMohamed, DaliaHashad, AmiraAttia, DaliaSalama, Maha MEl Bishbishy, Mahitab H2021-04-082021-04-082021-03https://doi.org/10.1016/j.biopha.2021.111537http://repository.msa.edu.eg/xmlui/handle/123456789/4499Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 23 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine me- tabolites. CSPE was standardized to a hesperidin content of 15.53 ± 0.152 mg% using RP-HPLC. It was suggested that the optimized formulation (F7) had (245 nm) particle size, (91.065%) EE, and (91.385%) occlusive effect with a spherical and smooth surface. The visible appearance of UV-induced photoaging in mice was significantly improved after topical application on CSPE-NLC cream for 5 weeks, levels of collagen and SOD were significantly increased in CSPE- NLC group, while levels of PGE2, COX2, JNK, MDA, and elastin was reduced. Finally, The prepared anti-aging CSPE-NLC cream represents a safe, convenient, and promising skincare cosmetic product.en-USSkin agingLipid nanoparticlesFactorial DesignElastaseCollagenaseCitrus sinensis L.Articlehttps://doi.org/10.1016/j.biopha.2021.111537