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However, in order to get desirable results, treatments with NSAIDs may take weeks, causing undesirable side effects and requiring repeated administration. In this sense, this work describes the development of an optimized nanostructured lipid carrier (NLC) formulation for intra-articular administration of naproxen (NPX). An experimental design (2\n                    <jats:sup>3<\/jats:sup>\n                    ) selected the best formulation in terms of its physicochemical and structural properties, elucidated by different methods (DLS, NTA, TEM, DSC, and ATR-FTIR). The chosen formulation (NLC-NPX) was tested on acute inflammatory TMJ nociception, in a rat model. The optimized excipients composition provided higher NPX encapsulation efficiency (99.8%) and the nanoparticles were found stable during 1 year of storage at 25\u2009\u00b0C.\n                    <jats:italic>In vivo<\/jats:italic>\n                    results demonstrated that the sustained delivery of NPX directly in the TMJ significantly reduced leukocytes migration and levels of pro-inflammatory cytokines (IL-1\u03b2 and TNF-\u03b1), for more than a week. These results point out the NLC-NPX formulation as a promising candidate for the safe treatment of inflammatory pain conditions of TMJ or other joints.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-47486-w","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T06:02:43Z","timestamp":1564639363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration"],"prefix":"10.1038","volume":"9","author":[{"given":"Viviane A.","family":"Guilherme","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-5449","authenticated-orcid":false,"given":"L\u00edgia N. M.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C. 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