{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:50:18Z","timestamp":1773013818796,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic inflammatory disease with sulfasalazine (SSZ) extensively used for long-term treatment of both juvenile and adult RA. Its use is associated with adverse effects and toxicity due to its non-selective biodistribution. Macrophages play an important role in inflammatory processes. In order to target SSZ to macrophages in this work two microparticulate systems (MPs) are developed: SSZ-loaded PLGA MPs without and with \u03b1-tocopherol, with particle sizes lower than 5 \u03bcm and encapsulation efficiencies of 81.07 \u00b1 11% and 63.50 \u00b1 6.62%, respectively. Release of SSZ from MPs prepared with \u03b1-tocopherol was prolonged for 20 days. In RAW 264.7 cell macrophages MPs prepared with \u03b1-tocopherol were captured faster. Cell viability studies confirmed that SSZ-loaded MPs prepared without and with \u03b1-tocopherol did not produce cytotoxicity at the concentrations assayed. The anti-inflammatory activity of SSZ-loaded MPs was studied by quantifying interleukins IL-1, IL-6 and TNF-\u03b1 in macrophages. All formulations produced a significant reduction of cytokine concentrations after 24 and 72 h, indicating that release of SSZ from the MPs was able to inhibit the inflammatory response induced by lipopolysaccharide (LPS). Gene expression of IL-1, IL-6 and TNF-\u03b1 was decreased by SSZ-loaded MPs. SSZ-loaded MPs prepared with \u03b1-tocopherol will potentially allow increasing the residence time of SSZ in the synovial cavity, prolonging its duration of action, and reducing the adverse effects associated with its non-selective biodistribution.<\/jats:p>","DOI":"10.3390\/pharmaceutics13070951","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T11:01:38Z","timestamp":1624532498000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Sulfasalazine Microparticles Targeting Macrophages for the Treatment of Inflammatory Diseases Affecting the Synovial Cavity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9766-1125","authenticated-orcid":false,"given":"Monica-Carolina","family":"Villa-Hermosilla","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5556-061X","authenticated-orcid":false,"given":"Ana","family":"Fern\u00e1ndez-Carballido","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s\/n, 28040 Madrid, Spain"},{"name":"Institute of Industrial Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Hurtado","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Health Sciences, Faculty of Pharmacy, CEU San Pablo University, 28925 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Barcia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s\/n, 28040 Madrid, Spain"},{"name":"Institute of Industrial Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8722-8758","authenticated-orcid":false,"given":"Consuelo","family":"Montejo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Health Sciences, Faculty of Pharmacy, CEU San Pablo University, 28925 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Alonso","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Negro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s\/n, 28040 Madrid, Spain"},{"name":"Institute of Industrial Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"ref_1","unstructured":"Fauci, A.S., and Langford, C. 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