{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:45:35Z","timestamp":1770079535279,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil (CAPES)","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Fungal infections by Candida spp. are opportunistic and most often occur in individuals with some predisposing factor. Essential oils (EO) have anti-Candida potential, being a therapeutic alternative to be explored, especially for superficial and mucosal candidiasis. The objective was to analyze the synergistic potential between the EO of Citrus limon, Cupressus sempervirens, Litsea cubeba and Melaleuca alternifolia, and each of them with clotrimazole, to inhibit in vitro the formation and eradication of Candida spp. biofilms. Added to this, the survival of Caenorhabditis elegans was evaluated after exposure to EO, clotrimazole and their synergistic combinations. Anti-Candida activity was determined by microdilution for the substances alone and in EO\u2013EO and EO\u2013clotrimazole combinations. The combinations were performed by the checkerboard method, and the reduction in the metabolic activity of biofilms was determined by the viability of MTT\/menadione. C. elegans larvae survival was evaluated after 24 h of exposure to EO, clotrimazole and synergistic combinations. The minimum inhibitory concentration (MIC) of EO ranged from 500 to &gt;4000 \u00b5g\/mL. The lowest MIC (500 \u00b5g\/mL) was for C. sempervirens and L. cubeba on a C. krusei isolate; for clotrimazole, the MIC ranged from 0.015 to 0.5 \u00b5g\/mL. Biofilm inhibition and eradication both ranged from 1000 to &gt;4000 \u00b5g\/mL. The lethal concentration (LC50) of C. limon, L. cubeba and M. alternifolia was 2000 \u00b5g\/mL for C. elegans, while for C. sempervirens and clotrimazole, it was not determined within the concentration limits tested. In combination, more than 85% of the larvae survived M. alternifolia\u2013clotrimazole, M. alternifolia\u2013L. cubeba, C. sempervirens\u2013clotrimazole and C. sempervirens\u2013C. limon combinations. This study is the first, to our knowledge, to present a synergistic relationship of EO\u2013EO and EO\u2013clotrimazole combinations on Candida spp. biofilms.<\/jats:p>","DOI":"10.3390\/pharmaceutics14091872","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T01:51:57Z","timestamp":1662515517000},"page":"1872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Combining Essential Oils with Each Other and with Clotrimazole Prevents the Formation of Candida Biofilms and Eradicates Mature Biofilms"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-5700","authenticated-orcid":false,"given":"Rafael Alves da","family":"Silva","sequence":"first","affiliation":[{"name":"Post-Graduation Program in Health Sciences, Federal University of Uberl\u00e2ndia (UFU), Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagela Bernadelli Sousa","family":"Silva","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Applied Immunology and Parasitology (PIPA), Federal University of Uberl\u00e2ndia (UFU), Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-6878","authenticated-orcid":false,"given":"Carlos Henrique Gomes","family":"Martins","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Applied Immunology and Parasitology (PIPA), Federal University of Uberl\u00e2ndia (UFU), Uberl\u00e2ndia 38400-902, MG, Brazil"},{"name":"Institute of Biomedical Sciences (ICBIM), Federal University of Uberl\u00e2ndia (UFU), Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-5951","authenticated-orcid":false,"given":"Regina Helena","family":"Pires","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Health Promotion, University of Franca (UNIFRAN), Franca 14404-600, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise Von Dolinger de Brito","family":"R\u00f6der","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Health Sciences, Federal University of Uberl\u00e2ndia (UFU), Uberl\u00e2ndia 38400-902, MG, Brazil"},{"name":"Institute of Biomedical Sciences (ICBIM), Federal University of Uberl\u00e2ndia (UFU), Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-5754","authenticated-orcid":false,"given":"Reginaldo dos Santos","family":"Pedroso","sequence":"additional","affiliation":[{"name":"Technical School of Health (ESTES), Federal University of Uberl\u00e2ndia (UFU), Uberl\u00e2ndia 38400-902, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pfaller, M.A., Diekema, D.J., Turnidge, J.D., Castanheira, M., and Jones, R.N. 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