{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:07:03Z","timestamp":1779163623806,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation\u2014FAPESP","award":["2019\/09831-9"],"award-info":[{"award-number":["2019\/09831-9"]}]},{"name":"S\u00e3o Paulo Research Foundation\u2014FAPESP","award":["2019\/26821-7"],"award-info":[{"award-number":["2019\/26821-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>The Candida auris species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by C. auris. NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij\u00ae 58) and soy phosphatidylcholine as surfactant\/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB\/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA\/FCF\/CAr n\u00b0 29\/2021) and infected with Candida auris CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by C. auris can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative.<\/jats:p>","DOI":"10.3390\/jof10040253","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T13:39:56Z","timestamp":1711546796000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Potential Activity of Micafungin and Amphotericin B Co-Encapsulated in Nanoemulsion against Systemic Candida auris Infection in a Mice Model"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4573-5743","authenticated-orcid":false,"given":"Gabriel Davi","family":"Marena","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"},{"name":"Department of Drug and Medicines, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-5364","authenticated-orcid":false,"given":"Gabriela Corr\u00eaa","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"},{"name":"Department of Drug and Medicines, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1730-9947","authenticated-orcid":false,"given":"Alba","family":"Ruiz-Gait\u00e1n","sequence":"additional","affiliation":[{"name":"Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain"},{"name":"Department of Medical Microbiology, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovana Scaramal","family":"Onisto","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz Chiari Manzini","family":"Bugalho","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Let\u00edcia Maria Valente","family":"Genezini","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u00edra Oliveira Dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana L\u00edgia","family":"Blanco","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6698-0545","authenticated-orcid":false,"given":"Marlus","family":"Chorilli","sequence":"additional","affiliation":[{"name":"Department of Drug and Medicines, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tais Maria","family":"Bauab","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"ref_1","first-page":"103","article-title":"Invasive Candidiasis","volume":"30","author":"Pappas","year":"2018","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_2","unstructured":"(2024, January 20). CDC Tracking Candida auris: Candida auris Fungal Diseases CDC, Available online: https:\/\/www.cdc.gov\/fungal\/candida-auris\/index.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00029-17","DOI":"10.1128\/CMR.00029-17","article-title":"Candida auris: A Review of the Literature","volume":"31","author":"Taori","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/cid\/ciw691","article-title":"Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses","volume":"64","author":"Lockhart","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e00623-22","DOI":"10.1128\/msphere.00623-22","article-title":"Role of Microbiota in the Skin Colonization of Candida auris","volume":"8","author":"Tharp","year":"2023","journal-title":"mSphere"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Montoya, A.M. (2024). The Importance of Candida auris in Skin. Curr. Fungal Infect. Rep., 1\u20137.","DOI":"10.1007\/s12281-024-00487-3"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"820","DOI":"10.5943\/mycosphere\/13\/1\/10","article-title":"Infection Caused by Candida auris: State of the Art","volume":"13","author":"Marena","year":"2022","journal-title":"Mycosphere"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jhin.2021.11.004","article-title":"Colonization by Candida auris in Critically Ill Patients: Role of Cutaneous and Rectal Localization during an Outbreak","volume":"120","author":"Piatti","year":"2022","journal-title":"J. Hosp. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.2147\/DDDT.S185833","article-title":"An Insight into New Strategies to Combat Antifungal Drug Resistance","volume":"12","author":"Zheng","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"219035","DOI":"10.1155\/2014\/219035","article-title":"Physicochemical Characterization and Thermodynamic Studies of Nanoemulsion-Based Transdermal Delivery System for Fullerene","volume":"2014","author":"Ngan","year":"2014","journal-title":"Sci. World J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s13205-014-0214-0","article-title":"Nanoemulsion: An Advanced Mode of Drug Delivery System","volume":"5","author":"Jaiswal","year":"2015","journal-title":"3 Biotech"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jconrel.2017.03.008","article-title":"Nanoemulsion: Concepts, Development and Applications in Drug Delivery","volume":"252","author":"Singh","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100533","DOI":"10.1016\/j.colcom.2021.100533","article-title":"Nanoemulsions: Formulation, Characterization, Biological Fate, and Potential Role against COVID-19 and Other Viral Outbreaks","volume":"45","author":"Tayeb","year":"2021","journal-title":"Colloids Interface Sci. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s12281-010-0018-6","article-title":"Use of Antifungal Combination Therapy: Agents, Order, and Timing","volume":"4","author":"Johnson","year":"2010","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1038\/s41598-020-58203-3","article-title":"Improved Efficacy of Antifungal Drugs in Combination with Monoterpene Phenols against Candida auris","volume":"10","author":"Shaban","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1021\/ar200105p","article-title":"Liposomes: From a Clinically Established Drug Delivery System to a Nanoparticle Platform for Theranostic Nanomedicine","volume":"44","author":"Kostarelos","year":"2011","journal-title":"Acc. Chem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"myac090","DOI":"10.1093\/mmy\/myac090","article-title":"Anti-Candida auris Activity In Vitro and In Vivo of Micafungin Loaded Nanoemulsions","volume":"61","author":"Marena","year":"2023","journal-title":"Med. Mycol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103566","DOI":"10.1016\/j.jddst.2022.103566","article-title":"Development and Characterization of an Amphotericin B-Loaded Nanoemulsion Applied to Candida auris Biofilms Control","volume":"74","author":"Marena","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"151203","DOI":"10.1016\/j.scitotenv.2021.151023","article-title":"Galleria Mellonella for Systemic Assessment of Anti-Candida auris Using Amphotericin B Loaded in Nanoemulsion","volume":"807","author":"Marena","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e02154-17","DOI":"10.1128\/AAC.02154-17","article-title":"Pharmacodynamics of a Long-Acting Echinocandin, CD101, in a Neutropenic Invasive-Candidiasis Murine Model Using an Extended-Interval Dosing Design","volume":"62","author":"Lepak","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.15698\/mic2022.08.782","article-title":"The Rise of Candida auris: From Unique Traits to Co-Infection Potential","volume":"9","author":"Egger","year":"2022","journal-title":"Microbial Cell"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Abe, M., Katano, H., Nagi, M., Higashi, Y., Sato, Y., Kikuchi, K., Hasegawa, H., and Miyazaki, Y. (2020). Potency of Gastrointestinal Colonization and Virulence of Candida auris in a Murine Endogenous Candidiasis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0243223"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e01625-19","DOI":"10.1128\/AAC.01625-19","article-title":"Impact of Candida auris Infection in a Neutropenic Murine Model","volume":"64","author":"Torres","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1038\/s41467-022-31201-x","article-title":"Innate Immune Responses against the Fungal Pathogen Candida auris","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"917363","DOI":"10.3389\/fphar.2022.917363","article-title":"Therapeutic Efficacy of Carvacrol-Loaded Nanoemulsion in a Mouse Model of Schistosomiasis","volume":"13","author":"Xavier","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1080\/22221751.2020.1771218","article-title":"Comparison of in Vivo Pathogenicity of Four Candida auris Clades in a Neutropenic Bloodstream Infection Murine Model","volume":"9","author":"Borman","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1080\/08982104.2017.1281951","article-title":"Microemulsion for Topical Delivery of Fenoprofen Calcium: In Vitro and in Vivo Evaluation","volume":"28","author":"Farghaly","year":"2018","journal-title":"J. Liposome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijpharm.2017.04.013","article-title":"Unmet Clinical Needs in the Treatment of Systemic Fungal Infections: The Role of Amphotericin B and Drug Targeting","volume":"525","author":"Ballesteros","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.riam.2009.06.003","article-title":"Amphotericin B: Side Effects and Toxicity","volume":"26","year":"2009","journal-title":"Rev. Iberoam. Micol."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/10\/4\/253\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:19:18Z","timestamp":1760105958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/10\/4\/253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["jof10040253"],"URL":"https:\/\/doi.org\/10.3390\/jof10040253","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,27]]}}}