ORIGINAL RESEARCH article
Front. Med. Technol.
Sec. Pharmaceutical Innovation
Volume 7 - 2025 | doi: 10.3389/fmedt.2025.1675082
Orodispersible Films Containing Chestnut Shell Phenolics for Buccal Delivery: A Preclinical Approach for Oral Mucositis Prevention
Provisionally accepted
Ana Sofia Ferreira1Ana Margarida Silva1Catarina Macedo1
Emily Laveriano2Julián Lozano-Castellón2
Rosa Maria Lamuela Raventós2Jaroslava Švarc-Gajíc3Paulo Costa4
Cristina Delerue-Matos1
Francisca Rodrigues4,5*- 1REQUIMTE LAQV Porto, Porto, Portugal
- 2Universitat de Barcelona, Barcelona, Spain
- 3Pravni Fakultet Novi Sad, Novi Sad, Serbia
- 4Faculty of Pharmacy, University of Porto, Porto, Portugal
- 5Universidade do Porto Faculdade de Farmacia, Porto, Portugal
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Introduction: Oral mucositis (OM) is a prevalent complication of cancer treatment that causes painful erythematous and ulcerated lesions in oral mucosa. Current treatments lack efficacy, being natural compounds explored as alternatives. Chestnut shells (CS) are rich in (poly)phenols with antioxidant, anti-inflammatory, and antitumor properties. This study aims to develop orodispersible films (OFs) with CS extract as active ingredient to manage OM. Methods: OFs, prepared by solvent casting and incorporating the CS extract, were characterized regarding physicochemical, antioxidant/antiradical, and anticancer properties, as well as bioactive compounds permeation through in vitro and ex vivo buccal models. Results: OFs revealed excellent features: thickness (125 µm), tensile strength (43.05 MPa), elongation (75.28%), weight (19 mg/cm2), moisture content (4.25%), and disintegration time (20.43 min). Significant antioxidant/antiradical activities were observed (TPC=37.05 mg GAE/g film; DPPH=143.42 mg TE/g film; FRAP=0.142 µmol FSE/g film). LC-ESI-LTQ-Orbitrap-HRMS analysis confirmed the high permeation of sebacic acid, epicatechin, isorhamnetin, protocatechuic acid, and L-tyrosine across both models, while cytotoxicity assays in oral epithelial cell lines (HSC3 and TR146) demonstrated the cytocompatibility. Conclusion: CS-OFs offers a promising approach for preventing and treating OM, enhancing efficacy and patient comfort by delivering bioactive compounds directly to the oral mucosa.
Keywords: Chestnut shells, Oral Mucositis, Antioxidants, Solvent casting, Buccal in vitro model, Porcine mucosa ex vivo assay
Received: 28 Jul 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Ferreira, Silva, Macedo, Laveriano, Lozano-Castellón, Lamuela Raventós, Švarc-Gajíc, Costa, Delerue-Matos and Rodrigues. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Francisca Rodrigues, Faculty of Pharmacy, University of Porto, Porto, Portugal
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.