{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:35:40Z","timestamp":1792089340598,"version":"4.4.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"The current study was approved & supported by North Khorasan University of Medical Sciences with Reg. No.","award":["4020335"],"award-info":[{"award-number":["4020335"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-33229-7","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T18:52:54Z","timestamp":1766083974000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanostructured lipid carriers for l-carnitine delivery: physicochemical characterization and effects on asthenozoospermic sperm function in vitro"],"prefix":"10.1038","volume":"16","author":[{"given":"Aniseh Mardanpoor","family":"Moghadam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Fathi-karkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh Tanhaye Kalate","family":"Sabz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Shariatnia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"issue":"2","key":"33229_CR1","doi-asserted-by":"publisher","first-page":"hoae017","DOI":"10.1093\/hropen\/hoae017","volume":"2024","author":"CJ De Jonge","year":"2024","unstructured":"De Jonge, C. J. et al. Current global status of male reproductive health. Hum. Reprod. open. 2024 (2), hoae017 (2024).","journal-title":"Hum. Reprod. open."},{"issue":"1","key":"33229_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s43032-020-00408-y","volume":"29","author":"R Dcunha","year":"2022","unstructured":"Dcunha, R. et al. Current insights and latest updates in sperm motility and associated applications in assisted reproduction. Reproductive Sci. 29 (1), 7\u201325 (2022).","journal-title":"Reproductive Sci."},{"issue":"3","key":"33229_CR3","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1007\/s43032-021-00801-1","volume":"29","author":"P Vogiatzi","year":"2022","unstructured":"Vogiatzi, P. et al. Male age and progressive sperm motility are critical factors affecting embryological and clinical outcomes in oocyte donor ICSI cycles. Reproductive Sci. 29 (3), 883\u2013895 (2022).","journal-title":"Reproductive Sci."},{"issue":"2","key":"33229_CR4","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3390\/antiox9020134","volume":"9","author":"K Nowicka-Bauer","year":"2020","unstructured":"Nowicka-Bauer, K. & Nixon, B. Molecular changes induced by oxidative stress that impair human sperm motility. Antioxidants 9 (2), 134 (2020).","journal-title":"Antioxidants"},{"issue":"2","key":"33229_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1071\/RD15325","volume":"28","author":"RJ Aitken","year":"2016","unstructured":"Aitken, R. J., Gibb, Z., Baker, M. A., Drevet, J. & Gharagozloo, P. Causes and consequences of oxidative stress in spermatozoa. Reprod. Fertility Dev. 28 (2), 1\u201310 (2016).","journal-title":"Reprod. Fertility Dev."},{"issue":"1","key":"33229_CR6","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3390\/antiox10010092","volume":"10","author":"R Chianese","year":"2021","unstructured":"Chianese, R. & Pierantoni, R. Mitochondrial reactive oxygen species (ROS) production alters sperm quality. Antioxidants 10 (1), 92 (2021).","journal-title":"Antioxidants"},{"issue":"1","key":"33229_CR7","first-page":"9540142","volume":"2016","author":"CS Opuwari","year":"2016","unstructured":"Opuwari, C. S. & Henkel, R. R. An update on oxidative damage to spermatozoa and oocytes. Biomed. Res. Int. 2016 (1), 9540142 (2016).","journal-title":"Biomed. Res. Int."},{"issue":"10","key":"33229_CR8","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.3390\/medicina59101769","volume":"59","author":"A Kaltsas","year":"2023","unstructured":"Kaltsas, A. Oxidative stress and male infertility: the protective role of antioxidants. Medicina 59 (10), 1769 (2023).","journal-title":"Medicina"},{"issue":"5","key":"33229_CR9","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.3390\/ijms23052717","volume":"23","author":"MA Virmani","year":"2022","unstructured":"Virmani, M. A. & Cirulli, M. The role of l-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Int. J. Mol. Sci. 23 (5), 2717 (2022).","journal-title":"Int. J. Mol. Sci."},{"issue":"2","key":"33229_CR10","first-page":"74","volume":"13","author":"M Modanloo","year":"2019","unstructured":"Modanloo, M. & Shokrzadeh, M. Analyzing mitochondrial dysfunction, oxidative stress, and apoptosis: potential role of L-carnitine. Iran. J. Kidney Dis. 13 (2), 74 (2019).","journal-title":"Iran. J. Kidney Dis."},{"key":"33229_CR11","unstructured":"Iliceto, M. The impact of L-carnitine on human semen quality upon cryopreservation, its association with sperm fatty acids, and assessment of a novel analytical tool for DNA fragmentation in mammals. (2025)."},{"issue":"2","key":"33229_CR12","first-page":"69","volume":"24","author":"L Kooshesh","year":"2023","unstructured":"Kooshesh, L., Nateghian, Z. & Aliabadi, E. Evaluation of L-carnitine potential in improvement of male fertility. J. Reprod. Infertility. 24 (2), 69 (2023).","journal-title":"J. Reprod. Infertility"},{"issue":"6","key":"33229_CR13","doi-asserted-by":"publisher","first-page":"e13267","DOI":"10.1111\/and.13267","volume":"51","author":"S Micic","year":"2019","unstructured":"Micic, S. et al. Double\u2010blind, randomised, placebo\u2010controlled trial on the effect of L\u2010carnitine and L\u2010acetylcarnitine on sperm parameters in men with idiopathic oligoasthenozoospermia. Andrologia 51 (6), e13267 (2019).","journal-title":"Andrologia"},{"issue":"2","key":"33229_CR14","doi-asserted-by":"publisher","first-page":"147","DOI":"10.4103\/japtr.japtr_46_23","volume":"14","author":"NKH Alyasari","year":"2023","unstructured":"Alyasari, N. K. H. & Selman, W. H. L-carnitine-loaded nanoparticle ameliorates cypermethrin-induced reproductive toxicity in adult male rats. J. Adv. Pharm. Tech. Res. 14 (2), 147\u2013154 (2023).","journal-title":"J. Adv. Pharm. Tech. Res."},{"issue":"20","key":"33229_CR15","doi-asserted-by":"publisher","first-page":"7115","DOI":"10.3390\/molecules28207115","volume":"28","author":"B Uner","year":"2023","unstructured":"Uner, B. et al. Assessing the in vitro and in vivo performance of L-carnitine-loaded nanoparticles in combating obesity. Molecules 28 (20), 7115 (2023).","journal-title":"Molecules"},{"key":"33229_CR16","doi-asserted-by":"publisher","first-page":"106420","DOI":"10.1016\/j.jddst.2024.106420","volume":"102","author":"AM Moghadam","year":"2024","unstructured":"Moghadam, A. M. et al. Nanoparticle-mediated L-carnitine delivery for improved male fertility. J. Drug Deliv. Sci. Technol. 102, 106420 (2024).","journal-title":"J. Drug Deliv. Sci. Technol."},{"issue":"3\u20134","key":"33229_CR17","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.colsurfb.2005.08.005","volume":"45","author":"F-Q Hu","year":"2005","unstructured":"Hu, F-Q. et al. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf., B. 45 (3\u20134), 167\u2013173 (2005).","journal-title":"Colloids Surf., B"},{"issue":"3","key":"33229_CR18","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1080\/03639045.2021.1892745","volume":"47","author":"Z Saghafi","year":"2021","unstructured":"Saghafi, Z., Mohammadi, M., Mahboobian, M. M. & Derakhshandeh, K. Preparation, characterization, and in vivo evaluation of perphenazine-loaded nanostructured lipid carriers for oral bioavailability improvement. Drug Dev. Ind. Pharm. 47 (3), 509\u2013520 (2021).","journal-title":"Drug Dev. Ind. Pharm."},{"issue":"43","key":"33229_CR19","doi-asserted-by":"publisher","first-page":"6630","DOI":"10.2174\/1381612823666171115105721","volume":"23","author":"V Andonova","year":"2017","unstructured":"Andonova, V. & Peneva, P. Characterization methods for solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). Curr. Pharm. Design. 23 (43), 6630\u20136642 (2017).","journal-title":"Curr. Pharm. Design"},{"issue":"8","key":"33229_CR20","doi-asserted-by":"publisher","first-page":"397","DOI":"10.3390\/pharmaceutics11080397","volume":"11","author":"PA Makoni","year":"2019","unstructured":"Makoni, P. A., Wa Kasongo, K. & Walker, R. B. Short term stability testing of efavirenz-loaded solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Pharmaceutics 11 (8), 397 (2019).","journal-title":"Pharmaceutics"},{"issue":"2","key":"33229_CR21","doi-asserted-by":"publisher","first-page":"299","DOI":"10.12928\/pharmaciana.v9i2.13070","volume":"9","author":"R Rabima","year":"2019","unstructured":"Rabima, R. & Sari, M. P. Entrapment efficiency and drug loading of Curcumin nanostructured lipid carrier (NLC) formula. Pharmaciana 9 (2), 299\u2013306 (2019).","journal-title":"Pharmaciana"},{"issue":"4","key":"33229_CR22","first-page":"331","volume":"21","author":"P Hassanzadeh","year":"2017","unstructured":"Hassanzadeh, P., Arbabi, E., Rostami, F., Atyabi, F. & Dinarvand, R. Aerosol delivery of ferulic acid-loaded nanostructured lipid carriers: A promising treatment approach against the respiratory disorders. Physiol. Pharmacol. 21 (4), 331\u2013342 (2017).","journal-title":"Physiol. Pharmacol."},{"issue":"2","key":"33229_CR23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3390\/scipharm89020025","volume":"89","author":"AL Ajiboye","year":"2021","unstructured":"Ajiboye, A. L., Nandi, U., Galli, M. & Trivedi, V. Olanzapine loaded nanostructured lipid carriers via high shear homogenization and ultrasonication. Sci. Pharm. 89 (2), 25 (2021).","journal-title":"Sci. Pharm."},{"issue":"1","key":"33229_CR24","doi-asserted-by":"publisher","first-page":"45","DOI":"10.38001\/ijlsb.1569828","volume":"8","author":"Y Da\u011fl\u0131o\u011flu","year":"2025","unstructured":"Da\u011fl\u0131o\u011flu, Y. Assessing of antiradical and antioxidant activities of-carnitine, L-carnitine, coenzyme Q10 and beta carotene dietary supplements. Int. J. Life Sci. Biotechnol. 8 (1), 45\u201350 (2025).","journal-title":"Int. J. Life Sci. Biotechnol."},{"issue":"1","key":"33229_CR25","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1166\/jbn.2013.1473","volume":"9","author":"S Hackenberg","year":"2013","unstructured":"Hackenberg, S. et al. Functional responses of human adipose tissue-derived mesenchymal stem cells to metal oxide nanoparticles in vitro. J. Biomed. Nanotechnol. 9 (1), 86\u201395 (2013).","journal-title":"J. Biomed. Nanotechnol."},{"issue":"Supplement_1","key":"33229_CR26","doi-asserted-by":"publisher","first-page":"deae108","DOI":"10.1093\/humrep\/deae108.403","volume":"39","author":"M Boussabbeh","year":"2024","unstructured":"Boussabbeh, M. et al. P-024 revitalizing male fertility: crocin\u2019s dual role in antioxidant mastery and mitochondrial activation to enhance sperm motility. Hum. Reprod. 39 (Supplement_1), deae108 (2024).","journal-title":"Hum. Reprod."},{"issue":"Supplement_1","key":"33229_CR27","doi-asserted-by":"publisher","first-page":"deae108","DOI":"10.1093\/humrep\/deae108.365","volume":"39","author":"R Lafuente","year":"2024","unstructured":"Lafuente, R. et al. O-308 is AI the future of sperm quality assessment? A comparative study of AI-enhanced and conventional semen analysis systems. Hum. Reprod. 39 (Supplement_1), deae108 (2024).","journal-title":"Hum. Reprod."},{"key":"33229_CR28","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Gupta, S. & Sharma, R. Eosin-nigrosin Staining procedure. Andrological Evaluation of Male Infertility: A Laboratory Guide p. 73\u201377 (Springer, 2016).","DOI":"10.1007\/978-3-319-26797-5_8"},{"key":"33229_CR29","doi-asserted-by":"crossref","unstructured":"Moskovtsev, S. I. & Librach, C. L. Methods of Sperm Vitality assessment. Spermatogenesis: Methods and Protocols p. 13\u201319 (Springer, 2012).","DOI":"10.1007\/978-1-62703-038-0_2"},{"issue":"4","key":"33229_CR30","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.fertnstert.2004.11.089","volume":"84","author":"JL Fern\u00e1ndez","year":"2005","unstructured":"Fern\u00e1ndez, J. L. et al. Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test. Fertil. Steril. 84 (4), 833\u2013842 (2005).","journal-title":"Fertil. Steril."},{"issue":"3","key":"33229_CR31","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/and.12259","volume":"47","author":"G Anifandis","year":"2015","unstructured":"Anifandis, G. et al. Sperm DNA fragmentation measured by H alosperm does not impact on embryo quality and ongoing pregnancy rates in IVF\/ICSI treatments. Andrologia 47 (3), 295\u2013302 (2015).","journal-title":"Andrologia"},{"issue":"1","key":"33229_CR32","doi-asserted-by":"publisher","first-page":"e180","DOI":"10.1111\/j.1365-2605.2009.00987.x","volume":"33","author":"A Amaral","year":"2010","unstructured":"Amaral, A. & Ramalho-Santos, J. Assessment of mitochondrial potential: implications for the correct monitoring of human sperm function. Int. J. Androl. 33 (1), e180\u2013e6 (2010).","journal-title":"Int. J. Androl."},{"issue":"6","key":"33229_CR33","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.3390\/pharmaceutics15061593","volume":"15","author":"C Viegas","year":"2023","unstructured":"Viegas, C. et al. Solid lipid nanoparticles vs. nanostructured lipid carriers: a comparative review. Pharmaceutics 15 (6), 1593 (2023).","journal-title":"Pharmaceutics"},{"issue":"8","key":"33229_CR34","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1208\/s12249-020-01852-4","volume":"21","author":"M Ya\u015facan","year":"2020","unstructured":"Ya\u015facan, M. et al. Polymeric nanoparticle versus liposome formulations: comparative physicochemical and metabolomic studies as l-carnitine delivery systems. Aaps Pharmscitech. 21 (8), 308 (2020).","journal-title":"Aaps Pharmscitech"},{"issue":"1","key":"33229_CR35","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3109\/10717540903431586","volume":"17","author":"L-J Jia","year":"2010","unstructured":"Jia, L-J. et al. Preparation and characterization of silybin-loaded nanostructured lipid carriers. Drug Deliv. 17 (1), 11\u201318 (2010).","journal-title":"Drug Deliv."},{"issue":"7","key":"33229_CR36","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1080\/03639045.2019.1569026","volume":"45","author":"UA Shinde","year":"2019","unstructured":"Shinde, U. A., Parmar, S. J. & Easwaran, S. Metronidazole-loaded nanostructured lipid carriers to improve skin deposition and retention in the treatment of rosacea. Drug Dev. Ind. Pharm. 45 (7), 1039\u20131051 (2019).","journal-title":"Drug Dev. Ind. Pharm."},{"issue":"4","key":"33229_CR37","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3390\/pharmaceutics13040531","volume":"13","author":"AC Ortiz","year":"2021","unstructured":"Ortiz, A. C., Ya\u00f1ez, O., Salas-Huenuleo, E. & Morales, J. O. Development of a nanostructured lipid carrier (NLC) by a low-energy method, comparison of release kinetics and molecular dynamics simulation. Pharmaceutics 13 (4), 531 (2021).","journal-title":"Pharmaceutics"},{"issue":"3","key":"33229_CR38","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3390\/pharmaceutics14030521","volume":"14","author":"H Yang","year":"2022","unstructured":"Yang, H. et al. Facile solvent-free Preparation of antioxidant idebenone-loaded nanoparticles for efficient wound healing. Pharmaceutics 14 (3), 521 (2022).","journal-title":"Pharmaceutics"},{"issue":"1","key":"33229_CR39","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12896-024-00845-6","volume":"24","author":"INAA Al-Fatlawi","year":"2024","unstructured":"Al-Fatlawi, I. N. A. A. et al. Effects of solid lipid nanocarrier containing Methyl urolithin A by coating folate-bound Chitosan and evaluation of its anti-cancer activity. BMC Biotechnol. 24 (1), 18 (2024).","journal-title":"BMC Biotechnol."},{"issue":"8","key":"33229_CR40","doi-asserted-by":"publisher","first-page":"633","DOI":"10.2217\/cer-2018-0128","volume":"8","author":"ME Nasab","year":"2019","unstructured":"Nasab, M. E., Takzaree, N., Saffari, P. M. & Partoazar, A. In vitro antioxidant activity and in vivo wound-healing effect of lecithin liposomes: a comparative study. J. Comp. Eff. Res. 8 (8), 633\u2013643 (2019).","journal-title":"J. Comp. Eff. Res."},{"issue":"1","key":"33229_CR41","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1080\/10942912.2020.1778027","volume":"23","author":"D-K Liu","year":"2020","unstructured":"Liu, D-K. et al. Evaluation of bioactive components and antioxidant capacity of four celery (Apium graveolens L.) leaves and petioles. Int. J. Food Prop. 23 (1), 1097\u20131109 (2020).","journal-title":"Int. J. Food Prop."},{"issue":"10","key":"33229_CR42","doi-asserted-by":"publisher","first-page":"e14199","DOI":"10.1111\/and.14199","volume":"53","author":"S Soares","year":"2021","unstructured":"Soares, S. et al. Nanocarried antioxidants in freezing extenders for Boar spermatozoa. Andrologia 53 (10), e14199 (2021).","journal-title":"Andrologia"},{"key":"33229_CR43","doi-asserted-by":"crossref","unstructured":"Walke, G., Gaurkar, S. S., Prasad, R., Lohakare, T. & Wanjari, M. The impact of oxidative stress on male reproductive function: exploring the role of antioxidant supplementation. Cureus ;15(7). (2023).","DOI":"10.7759\/cureus.42583"},{"key":"33229_CR44","doi-asserted-by":"crossref","unstructured":"Rhouma, M. B. et al. Oxidative stress and its correlation with sperm parameters in different semen quality groups. Korean J. Fertility Steril. (2025).","DOI":"10.5653\/cerm.2024.07668"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33229-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33229-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33229-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T13:11:03Z","timestamp":1769433063000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33229-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["33229"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-33229-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"assertion":[{"value":"8 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The present study was approved by the Ethics Committee of North Khorasan University of Medical Sciences, Bojnurd, Iran (approval code: IR.NKUMS.REC.1403.044). All procedures were conducted in accordance with the ethical standards of the institutional research committee and with the principles outlined in the Declaration of Helsinki. Written informed consent was obtained from all participants prior to semen sample collection. No identifiable personal information was recorded, and all samples were processed anonymously. AI tools were used for grammar and text enhancement, but the content was primarily authored by the writers.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"3375"}}