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Herein, a SEDDS loaded with lycopene purified from red guava (nanoLPG) was produced. The nanoemulsion was characterized using dynamic light scattering (DLS), zeta potential measurement, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), lycopene content quantification, radical scavenging activity and colloidal stability in cell culture medium. Then, in vivo toxicity and tissue distribution in orally treated mice and cytotoxicity on human prostate carcinoma cells (DU-145) and human peripheral blood mononuclear cells (PBMC) were evaluated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>NanoLPG exhibited physicochemical properties with a size around 200\u00a0nm, negative zeta-potential, and spherical morphology. The size, polydispersity index, and zeta potential parameters suffered insignificant alterations during the 12\u00a0month storage at 5\u00a0\u00b0C, which were associated with lycopene stability at 5\u00a0\u00b0C for 10\u00a0months. The nanoemulsion showed partial aggregation in cell culture medium at 37\u00a0\u00b0C after 24\u00a0h. NanoLPG at 0.10\u00a0mg\/mL exhibited radical scavenging activity equivalent to 0.043\u2009\u00b1\u20090.002\u00a0mg Trolox\/mL. The in vivo studies did not reveal any significant changes in clinical, behavioral, hematological, biochemical, and histopathological parameters in mice orally treated with nanoLPG at 10\u00a0mg\/kg for 28\u00a0days. In addition, nanoLPG successfully delivered lycopene to the liver, kidney and prostate in mice, improved its cytotoxicity against DU-145 prostate cancer cells\u2014probably by pathway independent on classical necrosis and apoptosis\u2014and did not affect PBMC viability.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Thus, nanoLPG stands as a promising and biosafe lycopene delivery system for further development of nanotechnology-based health products.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12645-021-00103-w","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T19:02:40Z","timestamp":1636311760000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Promising self-emulsifying drug delivery system loaded with lycopene from red guava (Psidium guajava L.): in vivo toxicity, biodistribution and cytotoxicity on DU-145 prostate cancer cells"],"prefix":"10.1186","volume":"12","author":[{"given":"Andreanne G.","family":"Vasconcelos","sequence":"first","affiliation":[]},{"given":"Ana Luisa A. 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