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This study evaluates the preclinical efficacy of curcumin-loaded bicosome systems (cur-BS) in mitigating chemotherapy-induced OM in mice. Methods: BS were prepared using a combination of 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), \u03b1-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 \u03bcM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5\u00d7) was selected for ex vivo permeability studies, release profile analysis, and in vitro anti-inflammatory efficacy. OM was induced in mice using 5-fluorouracil (5-FU) and acetic acid. Cur-BS 5\u00d7 was compared to the commercial product Dentoxol\u00ae. Results: The results showed that cur-BS 5\u00d7 provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5\u00d7 downregulated the expression of inflammatory markers (IL-1\u03b2 and TNF-\u03b1). Macroscopic assessments demonstrated that both cur-BS 5\u00d7 and Dentoxol\u00ae reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 \u00b1 0.5 for cur-BS 5\u00d7 and 1.0 \u00b1 0.0 for Dentoxol\u00ae, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5\u00d7, showing better epithelial structure and reduced inflammation. Cur-BS 5\u00d7-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol\u00ae group. Conclusions: These findings suggest that cur-BS 5\u00d7 may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol\u00ae.<\/jats:p>","DOI":"10.3390\/pharmaceutics17020181","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:36:32Z","timestamp":1738560992000},"page":"181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0654-2322","authenticated-orcid":false,"given":"Daniela","family":"Vergara","sequence":"first","affiliation":[{"name":"Center of Excellence in Translational Medicine\u2014Scientific Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Laboratory of Pharmaceutical and Cosmetic Bioproducts, Center of Excellence in Translational Medicine (CEMT), Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5558-5032","authenticated-orcid":false,"given":"Claudia","family":"Sanhueza","sequence":"additional","affiliation":[{"name":"Center for Resilience, Adaptation and Mitigation (CReAM), Universidad Mayor, Temuco 4780000, Chile"},{"name":"Escuela de Ingenier\u00eda, Facultad de Ciencias, Ingenier\u00eda y Tecnolog\u00eda, Universidad Mayor, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Medicine\u2014Scientific Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"Bustamante","sequence":"additional","affiliation":[{"name":"Center of Food Biotechnology and Bioseparations, Scientific and Technological Bioresource Nucleus BIOREN, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Vega","sequence":"additional","affiliation":[{"name":"Chemistry and Pharmacy Undergraduate Program Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7060-0656","authenticated-orcid":false,"given":"Francisca","family":"Acevedo","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Medicine\u2014Scientific Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Laboratory of Pharmaceutical and Cosmetic Bioproducts, Center of Excellence in Translational Medicine (CEMT), Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Chemical and Surfactant Technology, Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), C\/Jordi Girona 18-26, 08034 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1007\/s00520-019-04848-4","article-title":"Systematic review of basic oral care for the management of oral mucositis in cancer patients and clinical practice guidelines","volume":"27","author":"Hong","year":"2019","journal-title":"Support. 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