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However, the molecular basis of this synergistic effect is barely understood. The low solubility of these drugs and their adverse effects hamper their efficacy on the treatment of inflammatory processes making nanoparticulated systems promising candidates to overcome these drawbacks. The aim of this work is the preparation of polymeric nanoparticles (NPs) that combine NAP and Dx in different concentrations, and the evaluation of the expression of key genes related to autoimmune diseases like CIA. To do so, self\u2010assembled polymeric NPs that incorporate covalently\u2010linked NAP and physically entrapped Dx are designed to have hydrodynamic properties that, according to bibliography, may improve retention and colocalization of both drugs at inflammation sites. The rapid uptake of NPs by macrophages is demonstrated using coumarine\u20106\u2010loaded NPs. Dx is efficiently encapsulated and in vitro biological studies demonstrate that the Dx\u2010loaded NAP\u2010bearing NPs are noncytotoxic and reduce lipopolysaccharide\u2010induced NO released levels at any of the tested concentrations. Moreover, at the molecular level, a significant synergistic reduction of <jats:italic>Il12b<\/jats:italic> transcript gene expression when combining Dx and NAP is demonstrated.<\/jats:p>","DOI":"10.1002\/mabi.202000002","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T13:04:51Z","timestamp":1589807091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Polymeric Nanoparticles that Combine Dexamethasone and Naproxen for the Synergistic Inhibition of <i>Il12b<\/i> Transcription in Macrophages"],"prefix":"10.1002","volume":"20","author":[{"given":"Eva","family":"Espinosa\u2010Cano","sequence":"first","affiliation":[{"name":"Biomaterials Group Institute of Polymer Science and Technology (ICTP\u2010CSIC)  Madrid 28006 Spain"},{"name":"Networking Biomedical Research Centre in Bioengineering Biomaterials and Nanomedicine (CIBER\u2010BBN)  Madrid 28029 Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7395-5754","authenticated-orcid":false,"given":"Maria Rosa","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Biomaterials Group Institute of Polymer Science and Technology (ICTP\u2010CSIC)  Madrid 28006 Spain"},{"name":"Networking Biomedical Research Centre in Bioengineering Biomaterials and Nanomedicine (CIBER\u2010BBN)  Madrid 28029 Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yadileiny","family":"Portilla","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, and NanoBiomedicine Initiative Spanish National Center for Biotechnology (CNB\u2010CSIC)  Madrid 28049 Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domingo F.","family":"Barber","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, and NanoBiomedicine Initiative Spanish National Center for Biotechnology (CNB\u2010CSIC)  Madrid 28049 Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio","family":"San Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Biomaterials Group Institute of Polymer Science and Technology (ICTP\u2010CSIC)  Madrid 28006 Spain"},{"name":"Networking Biomedical Research Centre in Bioengineering Biomaterials and Nanomedicine (CIBER\u2010BBN)  Madrid 28029 Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,18]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.117.075614"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.043"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1356498"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00070-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-016-0702-4"},{"key":"e_1_2_7_6_1","first-page":"1373","volume":"31","author":"Schiff M.","year":"2004","journal-title":"J. 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