{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T03:27:59Z","timestamp":1773199679059,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T00:00:00Z","timestamp":1582156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this work, we developed a solid lipid nanoparticle (SLN) formulation with (+)-limonene 1,2-epoxide and glycerol monostearate (Lim-SLNs), stabilized with Poloxamer\u00ae 188 in aqueous dispersion to modify the release profile of the loaded monoterpene derivative. We also evaluated the role of SLNs in lipid peroxidation and cytotoxicity in a spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (the HaCaT cell line). For the cell viability assay, the colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used. Lim-SLNs with a loading capacity and encapsulation efficiency of 0.39% and 63%, respectively, were produced by high pressure homogenization. A mean particle size of 194 \u00b1 3.4 nm and polydispersity index of 0.244 were recorded for the loaded Lim-SLNs, as compared to 203 \u00b1 1.5 nm (PI 0.213) for the non-loaded (blank) SLNs. The loading of the monoterpene derivative into glycerol monostearate SLNs fitted into the zero-order kinetics, and ameliorated both lipid peroxidation and cytotoxicity in a keratinocyte cell line. A promising formulation for antioxidant and anti-tumoral activities is here proposed.<\/jats:p>","DOI":"10.3390\/ijms21041449","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T08:59:47Z","timestamp":1582275587000},"page":"1449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["(+)-Limonene 1,2-Epoxide-Loaded SLNs: Evaluation of Drug Release, Antioxidant Activity, and Cytotoxicity in an HaCaT Cell Line"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-6017","authenticated-orcid":false,"given":"Eliana B.","family":"Souto","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy (FFUC), Department of Pharmaceutical Technology, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"CEB\u2014Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2603-1377","authenticated-orcid":false,"given":"Aleksandra","family":"Zielinska","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy (FFUC), Department of Pharmaceutical Technology, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}]},{"given":"Selma B.","family":"Souto","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hospital de S\u00e3o Jo\u00e3o, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7747-9107","authenticated-orcid":false,"given":"Alessandra","family":"Durazzo","sequence":"additional","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}]},{"given":"Massimo","family":"Lucarini","sequence":"additional","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-3327","authenticated-orcid":false,"given":"Antonello","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, 80131 Napoli, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-9914","authenticated-orcid":false,"given":"Am\u00e9lia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Biology and Environment (DeBA-ECVA), University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal"},{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2545-0967","authenticated-orcid":false,"given":"Atanas G.","family":"Atanasov","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, 23 Acad. G. Bonchev str., 1113 Sofia, Bulgaria"},{"name":"Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrz\u0119biec, 05-552 Magdalenka, Poland"},{"name":"Department of Pharmacognosy, University of Vienna, Althanstra\u00dfe 14, 1090 Vienna, Austria"},{"name":"Ludwig Boltzmann Institute for Digital Health and Patient Safety, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria"}]},{"given":"Conrado","family":"Marques","sequence":"additional","affiliation":[{"name":"Laboratory of Nanotechnology and Nanomedicine (LNMED), Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil"},{"name":"University of Tiradentes (UNIT), Industrial Biotechnology Program, Av. Murilo Dantas 300, Aracaju 49032-490, Brazil"},{"name":"Tiradentes Institute, 150 Mt Vernon St, Dorchester, MA 02125, USA"}]},{"given":"Luciana N.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Laboratory of Nanotechnology and Nanomedicine, Institute of Technology and Research, Aracaju SE 49032-490, Brazil"},{"name":"School of Pharmacy, University Tiradentes, Aracaju SE 49032-490, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-6612","authenticated-orcid":false,"given":"Patricia","family":"Severino","sequence":"additional","affiliation":[{"name":"Laboratory of Nanotechnology and Nanomedicine (LNMED), Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil"},{"name":"University of Tiradentes (UNIT), Industrial Biotechnology Program, Av. Murilo Dantas 300, Aracaju 49032-490, Brazil"},{"name":"Tiradentes Institute, 150 Mt Vernon St, Dorchester, MA 02125, USA"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2174\/1573407211666150915214425","article-title":"Piperine: A Comprehensive Review of Pre-Clinical and Clinical Investigations","volume":"11","author":"Chinta","year":"2015","journal-title":"Curr. Bioact. 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