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Sesamol is a phytochemical compound known for its anti-inflammatory activity and low toxicity. Therefore, this study reports the optimization of a guar gum hydrogel with enhanced physicochemical and microbiological stability, providing an effective dosage form for topical application of sesamol nanocapsules to treat irritant contact dermatitis. Methods: Nano-based hydrogel containing 1 mg\/g sesamol was prepared by adding the nanocapsule suspension to form a 2.5% (w\/v) guar gum dispersion. Dynamic rheological analysis indicates that the formulations exhibit a non-Newtonian flow with pseudoplastic behavior. Hydrogels were evaluated by Fourier-transformed infrared (FTIR) spectroscopy, and, following spectrum acquisition, an unsupervised chemometrics model was developed to identify crucial variables. Additionally, the physicochemical and microbiological stability of the hydrogel was evaluated over a 60-day period. Results: ATR-FTIR spectra of all hydrogels evaluated are very similar after preparation and 60 days of storage. However, it showed a slight increase in average diameter and PDI and decreased pH values after 60 days. Microbiological assessment demonstrated that the hydrogel met the requirements for the microbial count over 60 days. The dermatitis model was induced by repeated applications of croton oil in the right ears of mice. The effectiveness of the hydrogels was evaluated by assessing ear edema and migration of polymorphonuclear cells. The nano-based hydrogel exhibited anti-inflammatory properties similar to those of dexamethasone. Conclusions: Therefore, the nano-based hydrogel containing sesamol exhibits therapeutic potential for treating cutaneous inflammatory diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics17081029","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T08:09:35Z","timestamp":1754640575000},"page":"1029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Repeated Administration of Guar Gum Hydrogel Containing Sesamol-Loaded Nanocapsules Reduced Skin Inflammation in Mice in an Irritant Contact Dermatitis Model"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5185-6915","authenticated-orcid":false,"given":"Vinicius Costa","family":"Prado","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Tecnologia Farmac\u00eautica, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9112-5566","authenticated-orcid":false,"given":"Bruna Rafaela Fretag","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o Biofarmac\u00eautica e Controle de Qualidade, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kauani","family":"Moenke","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Tecnologia Farmac\u00eautica, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6927-470X","authenticated-orcid":false,"given":"Amanda Maccangnan","family":"Zamberlan","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o Biofarmac\u00eautica e Controle de Qualidade, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0155-098X","authenticated-orcid":false,"given":"Samuel Felipe","family":"Atuati","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia da Dor, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Centro de Ci\u00eancias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3137-8614","authenticated-orcid":false,"given":"Ana Clara Perazzio","family":"Assis","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia da Dor, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Centro de Ci\u00eancias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne da Silva","family":"Brum","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia da Dor, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Centro de Ci\u00eancias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"},{"name":"Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre CEP 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-1239","authenticated-orcid":false,"given":"Raul Edison Luna","family":"Lazo","sequence":"additional","affiliation":[{"name":"Centro de Estudos em Biofarm\u00e1cia, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Paran\u00e1, Curitiba CEP 80210-170, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8413-3710","authenticated-orcid":false,"given":"Andr\u00e9a In\u00eas Horn","family":"Adams","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o Biofarmac\u00eautica e Controle de Qualidade, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Centro de Ci\u00eancias da Sa\u00fade, 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