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Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP) as a means to modulate microglia response towards an anti-inflammatory and neuroprotective phenotype (M2). RA-NP were first confirmed to be internalized by N9 microglial cells; nanoparticles did not affect cell survival at concentrations below 100\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL. Then, immunocytochemical studies were performed to assess the expression of pro- and anti-inflammatory mediators. Our results show that RA-NP inhibited LPS-induced release of nitric oxide and the expression of inducible nitric oxide synthase and promoted arginase-1 and interleukin-4 production. Additionally, RA-NP induced a ramified microglia morphology (indicative of M2 state), promoting tissue viability, particularly neuronal survival, and restored the expression of postsynaptic protein-95 in organotypic hippocampal slice cultures exposed to an inflammatory challenge. RA-NP also proved to be more efficient than the free equivalent RA concentration. Altogether, our data indicate that RA-NP may be envisioned as a promising therapeutic agent for brain inflammatory diseases.<\/jats:p>","DOI":"10.1155\/2017\/6742427","type":"journal-article","created":{"date-parts":[[2017,8,23]],"date-time":"2017-08-23T21:01:45Z","timestamp":1503522105000},"page":"1-11","source":"Crossref","is-referenced-by-count":41,"title":["Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles"],"prefix":"10.1155","volume":"2017","author":[{"given":"Marta","family":"Machado-Pereira","sequence":"first","affiliation":[{"name":"Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marqu\u00eas d\u2019\u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0237-499X","authenticated-orcid":true,"given":"Tiago","family":"Santos","sequence":"additional","affiliation":[{"name":"Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua 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