{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:55:16Z","timestamp":1789516516071,"version":"build-2803163510"},"reference-count":96,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Annatto (Bixa orellana L.) is extensively used as food pigment worldwide. Recently, several studies have found it to have healing and antioxidant properties, as well as effective action against leishmaniasis. Therefore, the purpose of this study was to incorporate the oil obtained from annatto seeds into a nanostructured lipid carrier (NLC) and evaluate its physicochemical properties and biological activity against Leishmania major. Nanoparticles were prepared by the fusion-emulsification and ultrasonication method, with the components Synperonic\u2122 PE (PL) as the surfactant, cetyl palmitate (CP) or myristyl myristate (MM) as solid lipids, annatto oil (AO) (2% and 4%, w\/w) as liquid lipid and active ingredient, and ultra-pure water. Physicochemical and biological characterizations were carried out to describe the NLCs, including particle size, polydispersity index (PDI), and zeta potential (ZP) by dynamic light scattering (DLS), encapsulation efficiency (EE%), thermal behavior, X-ray diffraction (XRD), transmission electron microscopy (TEM), Electron Paramagnetic Resonance (EPR), cytotoxicity on BALB\/c 3T3 fibroblasts and immortalized human keratinocyte cells, and anti-leishmaniasis activity in vitro. Nanoparticles presented an average diameter of ~200 nm (confirmed by TEM results), a PDI of less than 0.30, ZP between \u221212.6 and \u221231.2 mV, and more than 50% of AO encapsulated in NLCs. Thermal analyses demonstrated that the systems were stable at high temperatures with a decrease in crystalline structure due to the presence of AOs (confirmed by XRD). In vitro, the anti-leishmania test displayed good activity in encapsulating AO against L. major. The results indicate that the oily fraction of Bixa orellana L. in NLC systems should be evaluated as a potential therapeutic agent against leishmaniasis.<\/jats:p>","DOI":"10.3390\/pharmaceutics13111912","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:04:46Z","timestamp":1636671886000},"page":"1912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Annatto Oil Loaded Nanostructured Lipid Carriers: A Potential New Treatment for Cutaneous Leishmaniasis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0171-2360","authenticated-orcid":false,"given":"Marianna Ara\u00fajo","family":"Ferreira","sequence":"first","affiliation":[{"name":"Laboratory of Drug Development, Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato Ferreira","family":"de Almeida J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Souza","family":"Onofre","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Federal University of Vi\u00e7osa (UFV), Vi\u00e7osa 36570-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Renata","family":"Casadei","sequence":"additional","affiliation":[{"name":"Institute of Physics, University of S\u00e3o Paulo, USP, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kleber Juvenal Silva","family":"Farias","sequence":"additional","affiliation":[{"name":"Academic Unit of Biology and Chemistry, Center of Education and Health, Cuit\u00e9 58175-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-6612","authenticated-orcid":false,"given":"Patricia","family":"Severino","sequence":"additional","affiliation":[{"name":"Institute of Technology and Research (ITP), Aracaju 49010-390, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo Flamarion","family":"de Oliveira Franco","sequence":"additional","affiliation":[{"name":"Phytotechnical Department, Brazilian Agricultural Research Corporation (EMBRAPA), Brasilia 70770-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Nervo","family":"Raffin","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Development, Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00falio Fl\u00e1vio Accioly","family":"de Lima e Moura","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Development, Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"de Melo Barbosa","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Development, Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.pt.2016.08.005","article-title":"Opportunities for integrated control of neglected tropical diseases that affect the skin","volume":"32","author":"Engelman","year":"2016","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0140-6736(16)30171-4","article-title":"Neglected tropical diseases: Progress towards addressing the chronic pandemic","volume":"389","author":"Molyneux","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.actatropica.2017.04.029","article-title":"Application of nanotechnology in treatment of leishmaniasis: A review","volume":"172","author":"Akbari","year":"2017","journal-title":"Acta Trop."},{"key":"ref_4","unstructured":"WHO (2016). 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