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However, its use is related to the rebound effect, rosacea, purple, and increased blood glucose levels. Nanotechnology approaches have emerged as strategies for drug delivery due to their advantages in improving therapeutic effects. To reduce dexamethasone-related adverse effects and improve the anti-inflammatory efficacy of treatments, we developed nanocarriers containing this corticosteroid and oleic acid. Nanocapsules and nanoemulsion presented dexamethasone content close to the theoretical value and controlled dexamethasone release in an in vitro assay. Gellan gum-based hydrogels were successfully prepared to employ the nanostructured systems. A permeation study employing porcine skin showed that hydrogels containing non-nanoencapsulated dexamethasone (0.025%) plus oleic acid (3%) or oleic acid (3%) plus dexamethasone (0.025%)-loaded nanocapsules provided a higher amount of dexamethasone in the epidermis compared to non-nanoencapsulated dexamethasone (0.5%). Hydrogels containing oleic acid plus dexamethasone-loaded nanocapsules effectively inhibited mice ear edema (with inhibitions of 89.26 \u00b1 3.77% and 85.11 \u00b1 2.88%, respectively) and inflammatory cell infiltration (with inhibitions of 49.58 \u00b1 4.29% and 27.60 \u00b1 11.70%, respectively). Importantly, the dexamethasone dose employed in hydrogels containing the nanocapsules that effectively inhibited ear edema and cell infiltration was 20-fold lower (0.025%) than that of non-nanoencapsulated dexamethasone (0.5%). Additionally, no adverse effects were observed in preliminary toxicity tests. Our study suggests that nanostructured hydrogel containing a reduced effective dose of dexamethasone could be a promising therapeutic alternative to treat inflammatory disorders with reduced or absent adverse effects. Additionally, testing our formulation in a clinical study on patients with skin inflammatory diseases would be very important to validate our study.<\/jats:p>","DOI":"10.3390\/pharmaceutics16020176","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T04:05:46Z","timestamp":1706241946000},"page":"176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Nath\u00e1li","family":"Pegoraro","sequence":"first","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mailine","family":"Gehrcke","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, Centre of Health Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Camponogara","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fialho","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-4577","authenticated-orcid":false,"given":"Let\u00edcia","family":"Cruz","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, Centre of Health Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil"},{"name":"Department of Biochemistry and Molecular Biology, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s40264-015-0339-z","article-title":"Drug-Induced Hyperglycaemia and Diabetes","volume":"38","author":"Fathallah","year":"2015","journal-title":"Drug Saf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41574-019-0212-8","article-title":"Topical Glucocorticoids and Risk of Type 2 Diabetes Mellitus","volume":"15","author":"Johns","year":"2019","journal-title":"Nat. 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