{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:06:58Z","timestamp":1788631618985,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/07314\u20101"],"award-info":[{"award-number":["2017\/07314\u20101"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/22996\u20101"],"award-info":[{"award-number":["2017\/22996\u20101"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The emergence of resistant fungal species and the toxicity of currently available antifungal drugs are relevant issues that require special consideration. Cyclodextrins inclusion complexes could optimize the antimicrobial activity of such drugs and create a controlled release system with few side effects. This study aimed to assess the in vitro toxicity and antifungal effectiveness of nystatin (Nys) and chlorhexidine (Chx) complexed or not with \u03b2\u2010cyclodextrin (\u03b2CD). First, a drug toxicity screening was performed through the <jats:styled-content style=\"fixed-case\"><jats:italic>Artemia salina<\/jats:italic><\/jats:styled-content> bioassay. Then, the minimum inhibitory concentrations (MICs) against <jats:styled-content style=\"fixed-case\"><jats:italic>Candida albicans<\/jats:italic><\/jats:styled-content> were determined with the broth microdilution test. After MICs determination, the cytotoxicity of the drugs was evaluated through the methyl\u2010thiazolyl\u2010tetrazolium (MTT) and neutral red (NR) assays and through cell morphology analysis. The PROBIT analysis was used to determine the median lethal concentration (LC<jats:sub>50<\/jats:sub>), and the cell viability values were submitted to one\u2010way analysis of variance(ANOVA)\/Tukey (<jats:italic>\u03b1<\/jats:italic>\u2009=\u20090.05). Overall, the \u03b2CD\u2010complexed antifungals were less toxic against <jats:styled-content style=\"fixed-case\"><jats:italic>A.\u00a0salina<\/jats:italic><\/jats:styled-content> than their raw forms, suggesting that inclusion complexes can reduce the toxicity of drugs. The MICs obtained were as follows: Nys 0.5\u00a0mg\/L; Nys:\u03b2CD 4\u00a0mg\/L; Chx 4\u00a0mg\/L; and Chx:\u03b2CD 8\u00a0mg\/L. Chx showed significant cytotoxicity (MTT: 12.9\u2009\u00b1\u20099.6%; NR: 10.6\u2009\u00b1\u200912.5%) and promoted important morphological changes. Cells exposed to the other drugs showed viability above 70% with no cellular damage. These results suggest that antifungals complexed with \u03b2CD might be a biocompatible option for the treatment of <jats:italic>Candida<\/jats:italic>\u2010related infections.<\/jats:p>","DOI":"10.1002\/jat.4575","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T17:58:32Z","timestamp":1704909512000},"page":"747-755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anti\u2010<i>Candida<\/i> activity and in vitro toxicity screening of antifungals complexed with \u03b2\u2010cyclodextrin"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0777-5012","authenticated-orcid":false,"given":"Gustavo Sim\u00e3o","family":"Moraes","sequence":"first","affiliation":[{"name":"Department of Dentistry State University of Ponta Grossa  Ponta Grossa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaly Mayer","family":"Tozetto","sequence":"additional","affiliation":[{"name":"Department of Dentistry State University of Ponta Grossa  Ponta Grossa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaynara Aparecida Alves","family":"Pedroso","sequence":"additional","affiliation":[{"name":"Department of Dentistry State University of Ponta Grossa  Ponta Grossa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela Alves","family":"de Mattos","sequence":"additional","affiliation":[{"name":"Department of Dentistry State University of Ponta Grossa  Ponta Grossa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Migliorini","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Federal University of Parana  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia Sabrina","family":"Paludo","sequence":"additional","affiliation":[{"name":"Department of Structural, Molecular, and Genetic Biology, State University of Ponta Grossa  Ponta Grossa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio Andr\u00e9","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Dentistry State University of Ponta Grossa  Ponta Grossa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin Hermana","family":"Neppelenbroek","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics and Periodontics, Bauru School of Dentistry University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Migliorini","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Dentistry State University of Ponta Grossa  Ponta Grossa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970-9185.155140"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fdmed.2021.648547"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1754.2006.00871.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00069-19"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof3040057"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17101643"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008x(77)90191-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2007.09.012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1977.48.4.212"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijheh.2006.09.001"},{"key":"e_1_2_8_12_1","first-page":"89","article-title":"Chlorhexidine gluconate ingestion resulting in fatal respiratory distress syndrome","volume":"44","author":"Hirata K.","year":"2002","journal-title":"Veterinary and Human Toxicology"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks284"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1081\/clt-100102884"},{"key":"e_1_2_8_15_1","volume-title":"10993\u20135: 2009 biological evaluation of medical devices\u2014Part 5: Tests for in vitro cytotoxicity","author":"ISO, I","year":"2009"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.15698\/mic2020.06.718"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-016-2145-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(73)90135-0"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2017.1270264"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1590\/s1678-77572010000100010"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1078\/0944-7113-00044"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S100795"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(82)91018-2"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-971236"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.123.3194.464"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12917"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0123709"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480540500408416"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30316-X"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.75"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.67.784.210-a"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1201-9712(02)90154-2"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4155\/tde-2022-0068"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00094"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matchemphys.2019.122117"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01935.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3109\/10717544.2013.879679"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1517-83822012000200047"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2016.1199272"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.52.900"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr970025p"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567201820666221017103119"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myz012"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2021.635507"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.1662"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327111400104"},{"key":"e_1_2_8_48_1","first-page":"35","article-title":"Measuring cytotoxicity: A new perspective on LC50","volume":"27","author":"Zhang M.","year":"2007","journal-title":"Anticancer Research"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5173(94)90083-3"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4575","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:40:41Z","timestamp":1760539241000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,10]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/jat.4575"],"URL":"https:\/\/doi.org\/10.1002\/jat.4575","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,10]]},"assertion":[{"value":"2023-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}