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Conventional therapy has been linked to high recurrence, toxicity, and fungal resistance, necessitating the search for new drugs and delivery systems. In this study, caffeic acid phenethyl ester (CAPE) and gellan gum (GG) were studied as an antifungal agent and carrier system, respectively. First, we observed that different GG formulations (0.6 to 1.0% wt\/vol) were able to incorporate and release CAPE, reaching a controlled and prolonged release over 180 min at 1.0% of GG. CAPE-GG formulations exhibited antifungal activity at CAPE concentrations ranging from 128 to &gt;512 \u00b5g\/mL. Furthermore, CAPE-GG formulations significantly decreased the fungal viability of C. albicans biofilms at short times (12 h), mainly at 1.0% of GG (p &lt; 0.001). C. albicans protease activity was also reduced after 12 h of treatment with CAPE-GG formulations (p &lt; 0.001). Importantly, CAPE was not cytotoxic to human keratinocytes, and CAPE-GG formulations at 1.0% decreased the fungal burden (p = 0.0087) and suppressed inflammation in a rat model of denture stomatitis. Altogether, these results indicate that GG is a promising delivery system for CAPE, showing effective activity against C. albicans and potential to be used in the treatment of denture stomatitis.<\/jats:p>","DOI":"10.3390\/pharmaceutics16030298","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T07:50:26Z","timestamp":1708415426000},"page":"298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gellan-Based Hydrogel as a Drug Delivery System for Caffeic Acid Phenethyl Ester in the Treatment of Oral Candida albicans Infections"],"prefix":"10.3390","volume":"16","author":[{"given":"Ma\u00edra Terra","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3186-885X","authenticated-orcid":false,"given":"Paulo Henrique Fonseca do","family":"Carmo","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6690-9650","authenticated-orcid":false,"given":"L\u00edvia Mara Alves","family":"Figueiredo-Godoi","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia In\u00eas","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Dental Materials and Prosthodontics, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-0005","authenticated-orcid":false,"given":"Patr\u00edcia Michelle Nagai de","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"},{"name":"Center for Biomedical Engineering, School of Engineering, Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas de Paula","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9956-7768","authenticated-orcid":false,"given":"Luciane Dias de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5707-7565","authenticated-orcid":false,"given":"Alexandre Luiz Souto","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Dental Materials and Prosthodontics, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Shukla","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering, School of Engineering, Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-6856","authenticated-orcid":false,"given":"Juliana Campos","family":"Junqueira","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, S\u00e3o Paulo State University (UNESP), S\u00e3o Jos\u00e9 dos Campos 12245-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1093\/cid\/ciy776","article-title":"Estimation of Direct Healthcare Costs of Fungal Diseases in the United States","volume":"68","author":"Benedict","year":"2019","journal-title":"Clin. 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