Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis

Background/Objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. This study evaluates the preclinical efficacy of curcumin-loaded bicosome systems (cur-BS) in mitigating chemotherapy-induced OM in m...

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Main Authors: Daniela Vergara, Claudia Sanhueza, Susana Méndez, Mariela Bustamante, Benjamín Vega, Francisca Acevedo, Olga López
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/2/181
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author Daniela Vergara
Claudia Sanhueza
Susana Méndez
Mariela Bustamante
Benjamín Vega
Francisca Acevedo
Olga López
author_facet Daniela Vergara
Claudia Sanhueza
Susana Méndez
Mariela Bustamante
Benjamín Vega
Francisca Acevedo
Olga López
author_sort Daniela Vergara
collection DOAJ
description Background/Objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. 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), α-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 μM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5×) 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× was compared to the commercial product Dentoxol<sup>®</sup>. Results: The results showed that cur-BS 5× provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5× downregulated the expression of inflammatory markers (IL-1β and TNF-α). Macroscopic assessments demonstrated that both cur-BS 5× and Dentoxol<sup>®</sup> reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 ± 0.5 for cur-BS 5× and 1.0 ± 0.0 for Dentoxol<sup>®</sup>, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5×, showing better epithelial structure and reduced inflammation. Cur-BS 5×-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol<sup>®</sup> group. Conclusions: These findings suggest that cur-BS 5× may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol<sup>®</sup>.
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spelling doaj-art-a567ae3ffd6b4d43b1a663b533af4adb2025-08-20T02:44:50ZengMDPI AGPharmaceutics1999-49232025-02-0117218110.3390/pharmaceutics17020181Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral MucositisDaniela Vergara0Claudia Sanhueza1Susana Méndez2Mariela Bustamante3Benjamín Vega4Francisca Acevedo5Olga López6Center of Excellence in Translational Medicine—Scientific Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, ChileCenter for Resilience, Adaptation and Mitigation (CReAM), Universidad Mayor, Temuco 4780000, ChileCenter of Excellence in Translational Medicine—Scientific Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, ChileCenter of Food Biotechnology and Bioseparations, Scientific and Technological Bioresource Nucleus BIOREN, Universidad de La Frontera, Temuco 4811230, ChileChemistry and Pharmacy Undergraduate Program Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, ChileCenter of Excellence in Translational Medicine—Scientific Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4811230, ChileDepartment of Chemical and Surfactant Technology, Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), C/Jordi Girona 18-26, 08034 Barcelona, SpainBackground/Objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. 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), α-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 μM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5×) 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× was compared to the commercial product Dentoxol<sup>®</sup>. Results: The results showed that cur-BS 5× provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5× downregulated the expression of inflammatory markers (IL-1β and TNF-α). Macroscopic assessments demonstrated that both cur-BS 5× and Dentoxol<sup>®</sup> reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 ± 0.5 for cur-BS 5× and 1.0 ± 0.0 for Dentoxol<sup>®</sup>, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5×, showing better epithelial structure and reduced inflammation. Cur-BS 5×-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol<sup>®</sup> group. Conclusions: These findings suggest that cur-BS 5× may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol<sup>®</sup>.https://www.mdpi.com/1999-4923/17/2/181curcuminbicosomesdelivery systemsex vivo skin permeationoral mucositis
spellingShingle Daniela Vergara
Claudia Sanhueza
Susana Méndez
Mariela Bustamante
Benjamín Vega
Francisca Acevedo
Olga López
Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis
Pharmaceutics
curcumin
bicosomes
delivery systems
ex vivo skin permeation
oral mucositis
title Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis
title_full Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis
title_fullStr Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis
title_full_unstemmed Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis
title_short Evaluation of Preclinical Efficacy of Curcumin-Loaded Bicosome Systems in Amelioration of Oral Mucositis
title_sort evaluation of preclinical efficacy of curcumin loaded bicosome systems in amelioration of oral mucositis
topic curcumin
bicosomes
delivery systems
ex vivo skin permeation
oral mucositis
url https://www.mdpi.com/1999-4923/17/2/181
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