{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T02:44:42Z","timestamp":1774061082234,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007691","name":"Universidade da Beira Interior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s13346-025-01897-7","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T09:58:45Z","timestamp":1750240725000},"page":"4795-4818","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimized intranasal delivery of segesterone acetate progestin to the brain using nanoemulsions and microemulsions"],"prefix":"10.1007","volume":"15","author":[{"given":"Carina","family":"Peres","sequence":"first","affiliation":[]},{"given":"Sara","family":"Meirinho","sequence":"additional","affiliation":[]},{"given":"Samille","family":"Ferreira da Silva","sequence":"additional","affiliation":[]},{"given":"Izamara","family":"Maocha","sequence":"additional","affiliation":[]},{"given":"Anabela","family":"Chiangalala","sequence":"additional","affiliation":[]},{"given":"Susana","family":"Alves Ferreira","sequence":"additional","affiliation":[]},{"given":"M\u00e1rcio","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Shimin","family":"Zhang","sequence":"additional","affiliation":[]},{"given":"Narender","family":"Kumar","sequence":"additional","affiliation":[]},{"given":"Regine","family":"Sitruk-Ware","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Caetano Oliveira","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Gaspar","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Palmeira-de-Oliveira","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Palmeira-de-Oliveira","sequence":"additional","affiliation":[]},{"given":"Gilberto","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Gra\u00e7a","family":"Baltazar","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-9191","authenticated-orcid":false,"given":"Adriana O.","family":"Santos","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"1897_CR1","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1210\/en.2016-1426","volume":"158","author":"N Kumar","year":"2017","unstructured":"Kumar N, Fagart J, Liere P, Mitchell SJ, Knibb AR, Petit-Topin I, et al. Nestorone\u00ae as a novel progestin for nonoral contraception: Structure-Activity relationships and brain metabolism studies. Endocrinology. 2017;158:170\u201382.","journal-title":"Endocrinology"},{"key":"1897_CR2","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/S0015-0282(16)45918-2","volume":"36","author":"EM Coutinho","year":"1981","unstructured":"Coutinho EM, Da Silva AR, Carreira CMV, Sivin I. Long-term contraception with a single implant of the progestin ST-1435. Fertil Steril. 1981;36:737\u201340.","journal-title":"Fertil Steril"},{"key":"1897_CR3","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1749-6632.1997.tb48522.x","volume":"828","author":"A Robbins","year":"1997","unstructured":"Robbins A, Bardin CW. Nestorone\u2122 progestin: the ideal progestin for use in controlled release delivery Systemsa. Annals of the new York. Acad Sci. 1997;828:38\u201346.","journal-title":"Acad Sci"},{"key":"1897_CR4","doi-asserted-by":"publisher","unstructured":"Tanaka M, Sokabe M, Asai M. Progesterone Receptor Agonist, Nestorone, Exerts Long-Term Neuroprotective Effects Against Permanent Focal Cerebral Ischemia in Adult and Aged Male Rats. Transl Stroke Res. 2024 [cited 2025 Mar 10]; Available from: https:\/\/link.springer.com\/https:\/\/doi.org\/10.1007\/s12975-024-01288-z","DOI":"10.1007\/s12975-024-01288-z"},{"key":"1897_CR5","doi-asserted-by":"crossref","unstructured":"El-Etr M, Akwa Y, Rame M, Schumacher M, Sitruk\u2010Ware R. Nestorone\u00ae, a 19nor\u2010progesterone derivative boosts remyelination in an animal model of demyelination. CNS Neurosci Ther. 2021;27:464\u20139.","DOI":"10.1111\/cns.13538"},{"key":"1897_CR6","doi-asserted-by":"publisher","first-page":"108760","DOI":"10.1016\/j.neuropharm.2021.108760","volume":"198","author":"M Fr\u00e9chou","year":"2021","unstructured":"Fr\u00e9chou M, Zhu X, Kumar N, Sitruk-Ware R, Schumacher M, Mattern C, et al. Sex differences in the cerebroprotection by Nestorone intranasal delivery following stroke in mice. Neuropharmacology. 2021;198:108760.","journal-title":"Neuropharmacology"},{"key":"1897_CR7","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.freeradbiomed.2022.03.020","volume":"183","author":"J-Y Lee","year":"2022","unstructured":"Lee J-Y, Castelli V, Kumar N, Sitruk-Ware R, Borlongan CV. Contraceptive drug, nestorone, enhances stem cell-mediated remodeling of the stroke brain by dampening inflammation and rescuing mitochondria. Free Radic Biol Med. 2022;183:138\u201345.","journal-title":"Free Radic Biol Med"},{"key":"1897_CR8","doi-asserted-by":"publisher","first-page":"101136","DOI":"10.1016\/j.yfrne.2024.101136","volume":"73","author":"R Sitruk-Ware","year":"2024","unstructured":"Sitruk-Ware R, Sussman H, Brinton R, Schumacher M, Singer P, Kumar N, et al. Nestorone (segesterone acetate) effects on neuroregeneration. Front Neuroendocr. 2024;73:101136.","journal-title":"Front Neuroendocr"},{"key":"1897_CR9","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.brainres.2018.09.022","volume":"1719","author":"M Tanaka","year":"2019","unstructured":"Tanaka M, Ogaeri T, Samsonov M, Sokabe M. Nestorone exerts long-term neuroprotective effects against transient focal cerebral ischemia in adult male rats. Brain Res. 2019;1719:288\u201396.","journal-title":"Brain Res"},{"key":"1897_CR10","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1097\/GME.0000000000001135","volume":"25","author":"S Chen","year":"2018","unstructured":"Chen S, Kumar N, Mao Z, Sitruk-Ware R, Brinton RD. Therapeutic progestin segesterone acetate promotes neurogenesis: implications for sustaining regeneration in female brain. Menopause. 2018;25:1138\u201351.","journal-title":"Menopause"},{"key":"1897_CR11","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/0010-7824(94)90073-6","volume":"50","author":"O Heikinheimo","year":"1994","unstructured":"Heikinheimo O, Noe G, Haukkamaa M, L\u00e4hteenm\u00e4ki P. The progestin ST 1435\u2014rapid metabolism in man. Contraception. 1994;50:275\u201389.","journal-title":"Contraception"},{"key":"1897_CR12","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/0010-7824(84)90098-2","volume":"30","author":"PLA L\u00e4hteenm\u00e4ki","year":"1984","unstructured":"L\u00e4hteenm\u00e4ki PLA. Intestinal absorption of ST-1435 in rats. Contraception. 1984;30:143\u201351.","journal-title":"Contraception"},{"key":"1897_CR13","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/0010-7824(93)90117-P","volume":"48","author":"G No\u00e9","year":"1993","unstructured":"No\u00e9 G, Salvatierra A, Heikinheimo O, Maturana X, Croxatto HB. Pharmacokinetics and bioavailability of ST 1435 administered by different routes. Contraception. 1993;48:548\u201356.","journal-title":"Contraception"},{"key":"1897_CR14","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0039-128X(00)00119-7","volume":"65","author":"N Kumar","year":"2000","unstructured":"Kumar N. Nestorone\u00ae: a progestin with a unique Pharmacological profile. Steroids. 2000;65:629\u201336.","journal-title":"Steroids"},{"key":"1897_CR15","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/S0039-128X(03)00140-5","volume":"68","author":"R Sitruk-Ware","year":"2003","unstructured":"Sitruk-Ware R, Small M, Kumar N, Tsong Y-Y, Sundaram K, Jackanicz T. Nestorone\u00ae: clinical applications for contraception and HRT. Steroids. 2003;68:907\u201313.","journal-title":"Steroids"},{"key":"1897_CR16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.jconrel.2018.12.049","volume":"295","author":"C Costa","year":"2019","unstructured":"Costa C, Moreira JN, Amaral MH, Sousa Lobo JM, Silva AC. Nose-to-brain delivery of lipid-based nanosystems for epileptic seizures and anxiety crisis. J Controlled Release. 2019;295:187\u2013200.","journal-title":"J Controlled Release"},{"key":"1897_CR17","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.jconrel.2016.07.001","volume":"237","author":"M Kapoor","year":"2016","unstructured":"Kapoor M, Cloyd JC, Siegel RA. A review of intranasal formulations for the treatment of seizure emergencies. J Controlled Release. 2016;237:147\u201359.","journal-title":"J Controlled Release"},{"key":"1897_CR18","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.3390\/pharmaceutics14071487","volume":"14","author":"S Meirinho","year":"2022","unstructured":"Meirinho S, Rodrigues M, Santos AO, Falc\u00e3o A, Alves G. Self-Emulsifying drug delivery systems: an alternative approach to improve brain bioavailability of poorly Water-Soluble drugs through intranasal administration. Pharmaceutics. 2022;14:1487.","journal-title":"Pharmaceutics"},{"key":"1897_CR19","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.3762\/bjnano.15.113","volume":"15","author":"S Akpinar Adscheid","year":"2024","unstructured":"Akpinar Adscheid S, T\u00fcreli AE, G\u00fcnday-T\u00fcreli N, Schneider M. Nanotechnological approaches for efficient N2B delivery: from small-molecule drugs to biopharmaceuticals. Beilstein J Nanotechnol. 2024;15:1400\u201314.","journal-title":"Beilstein J Nanotechnol"},{"key":"1897_CR20","doi-asserted-by":"publisher","first-page":"3311","DOI":"10.1111\/bcp.15828","volume":"89","author":"VG Tymko","year":"2023","unstructured":"Tymko VG, Tsapko GV, Kovalova KV, Mashchenko SV, Oliinykov DS, Kuznetsov IE. Comparative pharmacokinetics of Nalbuphine nasal spray and solution for injection in healthy volunteers. Brit J Clin Pharma. 2023;89:3311\u201323.","journal-title":"Brit J Clin Pharma"},{"key":"1897_CR21","doi-asserted-by":"publisher","first-page":"588","DOI":"10.3390\/pharmaceutics14030588","volume":"14","author":"PC Pires","year":"2022","unstructured":"Pires PC, Rodrigues M, Alves G, Santos AO. Strategies to improve drug strength in nasal preparations for brain delivery of low aqueous solubility drugs. Pharmaceutics. 2022;14:588.","journal-title":"Pharmaceutics"},{"key":"1897_CR22","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jconrel.2017.11.047","volume":"270","author":"PC Pires","year":"2018","unstructured":"Pires PC, Santos AO. Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies. J Controlled Release. 2018;270:89\u2013100.","journal-title":"J Controlled Release"},{"issue":"2025","key":"1897_CR23","first-page":"2479759","volume":"17425247","author":"F Laffleur","year":"2025","unstructured":"Laffleur F, Millotti G, Lagast J. An overview of oral bioavailability enhancement through self- emulsifying drug delivery systems. Expert Opin Drug Deliv. 2025;17425247(2025):2479759.","journal-title":"Expert Opin Drug Deliv"},{"key":"1897_CR24","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1007\/s11095-010-0309-1","volume":"28","author":"N Anton","year":"2011","unstructured":"Anton N, Vandamme TF. Nano-emulsions and Micro-emulsions: clarifications of the critical differences. Pharm Res. 2011;28:978\u201385.","journal-title":"Pharm Res"},{"key":"1897_CR25","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.ijpharm.2017.05.005","volume":"526","author":"SP Callender","year":"2017","unstructured":"Callender SP, Mathews JA, Kobernyk K, Wettig SD. Microemulsion utility in pharmaceuticals: implications for multi-drug delivery. Int J Pharm. 2017;526:425\u201342.","journal-title":"Int J Pharm"},{"key":"1897_CR26","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jconrel.2017.03.008","volume":"252","author":"Y Singh","year":"2017","unstructured":"Singh Y, Meher JG, Raval K, Khan FA, Chaurasia M, Jain NK, et al. Nanoemulsion: concepts, development and applications in drug delivery. J Controlled Release. 2017;252:28\u201349.","journal-title":"J Controlled Release"},{"key":"1897_CR27","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.3390\/pharmaceutics15071878","volume":"15","author":"PC Pires","year":"2023","unstructured":"Pires PC, Fernandes M, Nina F, Gama F, Gomes MF, Rodrigues LE, et al. Innovative aqueous nanoemulsion prepared by phase inversion emulsification with exceptional homogeneity. Pharmaceutics. 2023;15:1878.","journal-title":"Pharmaceutics"},{"key":"1897_CR28","doi-asserted-by":"publisher","first-page":"123145","DOI":"10.1016\/j.ijpharm.2023.123145","volume":"642","author":"S Meirinho","year":"2023","unstructured":"Meirinho S, Rodrigues M, Santos AO, Falc\u00e3o A, Alves G. Nose-to-brain delivery of perampanel formulated in a self-microemulsifying drug delivery system improves anticonvulsant and anxiolytic activity in mice. Int J Pharm. 2023;642:123145.","journal-title":"Int J Pharm"},{"key":"1897_CR29","doi-asserted-by":"publisher","first-page":"121853","DOI":"10.1016\/j.ijpharm.2022.121853","volume":"622","author":"S Meirinho","year":"2022","unstructured":"Meirinho S, Rodrigues M, Ferreira CL, Oliveira RC, Fortuna A, Santos AO, et al. Intranasal delivery of lipid-based nanosystems as a promising approach for brain targeting of the new-generation antiepileptic drug perampanel. Int J Pharm. 2022;622:121853.","journal-title":"Int J Pharm"},{"key":"1897_CR30","doi-asserted-by":"publisher","unstructured":"Gama F, Meirinho S, Pires PC, Tinoco J, Martins Gaspar MC, Baltazar G et al. Simvastatin is delivered to the brain by high-strength intranasal cationic SMEDDS and nanoemulsions. Drug Deliv and Transl Res. 2025 [cited 2025 Mar 9]; Available from: https:\/\/link.springer.com\/https:\/\/doi.org\/10.1007\/s13346-024-01769-6","DOI":"10.1007\/s13346-024-01769-6"},{"key":"1897_CR31","unstructured":"European Directorate for the Quality of Medicines. & HealthCare (EDQM). 5.1.3 Efficacy of antimicrobial preservation. 10th ed. European Pharmacopoeia. p. 625. Available from: https:\/\/pheur.edqm.eu\/home"},{"key":"1897_CR32","unstructured":"International Organization for Standardization. ISO 20776-1:2019 susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices\u2013 Part 1: broth micro-dilution reference method for testing the in vitro activity of antimicrobial agents against rapidly growing aerobic bacteria involved in infectious diseases. Geneva; 2019."},{"key":"1897_CR33","unstructured":"Guinea J, Meletiadis J, Arikan-Akdagli S, Giske C, Giske K, Arendrup M et al. EUCAST Definitive Document E.Def 7.4 Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts. [cited 2025 Mar 17]. Available from: https:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/AFST\/Files\/EUCAST_E.Def_7.4_Yeast_definitive_revised_2023.pdf"},{"key":"1897_CR34","unstructured":"NIH. ICCVAM-Recommended Test Method Protocol. Hen\u2019s Egg Test\u2013 Chorioallantoic Membrane (HET-CAM) Test Method. [cited 2025 Mar 17]. Available from: https:\/\/ntp.niehs.nih.gov\/sites\/default\/files\/iccvam\/docs\/protocols\/ivocular-hetcam.pdf"},{"key":"1897_CR35","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1111\/jnc.15740","volume":"164","author":"G Gava-Junior","year":"2023","unstructured":"Gava-Junior G, Ferreira SA, Roque C, Mendes-Oliveira J, Serrenho I, Pinto N, et al. High-frequency repetitive magnetic stimulation rescues ischemia-injured neurons through modulation of glial-derived neurotrophic factor present in the astrocyte\u2019s secretome. J Neurochem. 2023;164:813\u201328.","journal-title":"J Neurochem"},{"key":"1897_CR36","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.3390\/pharmaceutics16101333","volume":"16","author":"S Jacob","year":"2024","unstructured":"Jacob S, Kather FS, Boddu SHS, Shah J, Nair AB. Innovations in nanoemulsion technology: enhancing drug delivery for oral, parenteral, and ophthalmic applications. Pharmaceutics. 2024;16:1333.","journal-title":"Pharmaceutics"},{"key":"1897_CR37","doi-asserted-by":"publisher","first-page":"992","DOI":"10.3389\/fphar.2018.00992","volume":"9","author":"S Muke","year":"2018","unstructured":"Muke S, Kaikini A, Peshattiwar V, Bagle S, Dighe V, Sathaye S. Neuroprotective effect of coumarin nasal formulation: kindling model assessment of epilepsy. Front Pharmacol. 2018;9:992.","journal-title":"Front Pharmacol"},{"key":"1897_CR38","doi-asserted-by":"publisher","first-page":"495","DOI":"10.14573\/altex.1710091","volume":"35","author":"R Palmeira-de-Oliveira","year":"2018","unstructured":"Palmeira-de-Oliveira R, Monteiro Machado R, Martinez-de-Oliveira J, Palmeira-de-Oliveira A. Testing vaginal irritation with the hen\u2019s egg Test-Chorioallantoic membrane assay. Altex. 2018;35:495\u2013503.","journal-title":"Altex"},{"key":"1897_CR39","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.3390\/pharmaceutics13111750","volume":"13","author":"L Tratnjek","year":"2021","unstructured":"Tratnjek L, Sibinovska N, Kristan K, Kreft ME. In vitro ciliotoxicity and cytotoxicity testing of repeated chronic exposure to topical nasal formulations for safety studies. Pharmaceutics. 2021;13:1750.","journal-title":"Pharmaceutics"},{"key":"1897_CR40","doi-asserted-by":"publisher","first-page":"104865","DOI":"10.1016\/j.tiv.2020.104865","volume":"66","author":"L Tratnjek","year":"2020","unstructured":"Tratnjek L, Kreft M, Kristan K, Kreft ME. Ciliary beat frequency of in vitro human nasal epithelium measured with the simple high-speed microscopy is applicable for safety studies of nasal drug formulations. Toxicol in Vitro. 2020;66:104865.","journal-title":"Toxicol in Vitro"},{"key":"1897_CR41","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/0039-128X(95)00074-Z","volume":"60","author":"S Ahmed","year":"1995","unstructured":"Ahmed S. Accelerated stability studies on 16-methylene-17\u03b1-acetoxy-19-nor-pregn-4-ene-3,20-dione (Nestorone\u2122). Steroids. 1995;60:534\u20139.","journal-title":"Steroids"},{"key":"1897_CR42","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1007\/BF02931506","volume":"48","author":"M Marounek","year":"2003","unstructured":"Marounek M, Sk\u0159ivanov\u00e1 E, Rada V. Susceptibility OfEscherichia coli to C2-C18 fatty acids. Folia Microbiol. 2003;48:731\u20135.","journal-title":"Folia Microbiol"},{"key":"1897_CR43","doi-asserted-by":"publisher","first-page":"3488","DOI":"10.3168\/jds.S0022-0302(05)73033-2","volume":"88","author":"MKM Nair","year":"2005","unstructured":"Nair MKM, Joy J, Vasudevan P, Hinckley L, Hoagland TA, Venkitanarayanan KS. Antibacterial effect of caprylic acid and monocaprylin on major bacterial mastitis pathogens. J Dairy Sci. 2005;88:3488\u201395.","journal-title":"J Dairy Sci"},{"key":"1897_CR44","doi-asserted-by":"publisher","first-page":"291","DOI":"10.5650\/jos.ess18220","volume":"68","author":"T Watanabe","year":"2019","unstructured":"Watanabe T, Yamamoto Y, Miura M, Konno H, Yano S, Nonomura Y. Systematic analysis of selective bactericidal activity of fatty acids against Staphylococcus aureus with minimum inhibitory concentration and minimum bactericidal concentration. J Oleo Sci. 2019;68:291\u20136.","journal-title":"J Oleo Sci"},{"key":"1897_CR45","doi-asserted-by":"publisher","first-page":"255","DOI":"10.3314\/mmj.53.255","volume":"53","author":"M Takahashi","year":"2012","unstructured":"Takahashi M, Inoue S, Hayama K, Ninomiya K, Abe S. Inhibition of Candida mycelia growth by a medium chain fatty acids, capric acid in Vitoro and its therapeutic efficacy in murine oral candidiasis. Med Mycol J. 2012;53:255\u201361.","journal-title":"Med Mycol J"}],"container-title":["Drug Delivery and Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-025-01897-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13346-025-01897-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-025-01897-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T21:02:26Z","timestamp":1763413346000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13346-025-01897-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,18]]},"references-count":45,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["1897"],"URL":"https:\/\/doi.org\/10.1007\/s13346-025-01897-7","relation":{},"ISSN":["2190-393X","2190-3948"],"issn-type":[{"value":"2190-393X","type":"print"},{"value":"2190-3948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,18]]},"assertion":[{"value":"8 June 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All institutional and national guidelines for the care and use of laboratory animals were followed. The experimental protocols were reviewed and approved (reference 0421\/000\/000\/2023 002871) by the competent national authority [Portuguese General Directorate for Food and Veterinary (DGAV\u2013 Dire\u00e7\u00e3o Geral de Alimenta\u00e7\u00e3o e Veterin\u00e1ria)], in agreement with the regulations of the European Directive 2010\/63\/EU and Portuguese law (\n                      Decreto-Lei n\u00ba 113\/2013\n                      ).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"Adriana O. Santos and Gilberto Alves are inventors on a patent application related with the nanoemulsions described in this manuscript (WO2022259205A1), of which the US national stage application #18\/568,879 is pending to Population Council, NY, USA. Regine Sitruk-Ware is an inventor on the use of Nestorone for neuroprotection: United States patent number 9,446,051, to Sitruk-Ware, Schumacher, Brinton, El-Etr, Ghoumari and Guennoun, entitled, \u201cNeuroprotection and Myelin Repair Using Nestorone,\u201d filed December 21, 2012. Issued September 20, 2016; and United States patent number 10,052,335 to Sitruk-Ware, Schumacher, Brinton, El-Etr, Ghoumari and Guennoun, entitled, \u201cNeuroprotection and Myelin Repair Using Nestorone,\u201d filed October 19, 2010. Issued August 21, 2018. Ana Palmeira-de-Oliveira, Rita Palmeira-de-Oliveira own the company disclosed as their affiliation (Labfit-HPRD, Health Products Research and Development Lda, 6200\u2009\u2212\u2009284 Covilh\u00e3, Portugal.) and Carlos Gaspar is their employee. Authors Carina Peres, Sara Meirinho, Samille Ferreira da Silva, Izamara Maocha, Anabela Chiangalala, Susana Alves Ferreira, M\u00e1rcio Rodrigues, Shimin Zhang, Narender Kumar, Rui Caetano Oliveira and Gra\u00e7a Baltazar declare that they have no conflict of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}