{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:09:47Z","timestamp":1778832587614,"version":"3.51.4"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BDE\/3379\/5\/2009"],"award-info":[{"award-number":["SFRH\/BDE\/3379\/5\/2009"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/DTP\/04138\/2019"],"award-info":[{"award-number":["UID\/DTP\/04138\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04138\/2020"],"award-info":[{"award-number":["UIDB\/04138\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["CEECIND\/03143\/2017"],"award-info":[{"award-number":["CEECIND\/03143\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["CEECINST\/00145\/2018"],"award-info":[{"award-number":["CEECINST\/00145\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Innovative formulations, including solid lipid nanoparticles (SLNs), have been sought to improve skin permeation of non-steroidal anti-inflammatory drugs (NSAIDs). The present study explores the use of SLNs, prepared using a fusion-emulsification method, to increase skin permeation and in vivo activity of two relevant NSAIDs: A liquid molecule (etofenamate) and a solid one (ibuprofen), formulated in a 2% hydroxypropyl methylcellulose gel through the gelation of SLN suspensions. Compritol\u00ae 888 ATO and Tween\u00ae 80 were used as a solid lipid and a surfactant, respectively. All production steps were up scalable, resulting in SLNs with high encapsulation efficiency (&gt;90%), a mean particle size of &lt;250 nm, a polydispersity index &lt;0.2, and that were stable for 12 months. In vitro permeation, using human skin in Franz diffusion cells, showed increased permeation and similar cell viability in Df and HaCaT cell lines for SLN formulations when compared to commercial formulations of etofenamate (Reumon\u00ae Gel 5%) and ibuprofen (Ozonol\u00ae 5%). In vivo activity in the rat paw edema inflammation model showed that SLN hydrogels containing lower doses of etofenamate (8.3 times lower) and ibuprofen (16.6 times lower) produced similar effects compared to the commercial formulations, while decreasing edema and inflammatory cell infiltration, and causing no histological changes in the epidermis. These studies demonstrate that encapsulation in SLNs associated to a suitable hydrogel is a promising technological approach to NSAIDs dermal application.<\/jats:p>","DOI":"10.3390\/pharmaceutics13030328","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T20:29:48Z","timestamp":1614803388000},"page":"328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Increased Therapeutic Efficacy of SLN Containing Etofenamate and Ibuprofen in Topical Treatment of Inflammation"],"prefix":"10.3390","volume":"13","author":[{"given":"Giuliana","family":"Mancini","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"LEF, Laborat\u00f3rios de Estudos Farmac\u00eauticos, 2730-269 Barcarena, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-2740","authenticated-orcid":false,"given":"L\u00eddia M. D.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-5622","authenticated-orcid":false,"given":"Joana","family":"Marto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Filomena A.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Instituto de Medicina Molecular \u2018Jo\u00e3o Lobo Antunes\u2019, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Sandra","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2429-7991","authenticated-orcid":false,"given":"Helena Margarida","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7807-4726","authenticated-orcid":false,"given":"Ant\u00f3nio J.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00535-019-01657-8","article-title":"Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: A comprehensive review","volume":"55","author":"Watanabe","year":"2020","journal-title":"J. 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