170172 20260407115448.0 doi 10.1039/d5nh00782h sideral 148745 ART-2026-148745 eng Esteban-Pérez, Natalia Controlled release of glucocorticoid via PLGA nanoparticles for modulating macrophage polarization in inflammation situations 2026 Glucocorticoids are among the most widely used anti-inflammatory and immunosuppressive drugs. However, their prolonged administration is associated with a wide range of adverse side effects including long-lasting immunosuppression. In this study, we aimed to encapsulate two commonly used glucocorticoids with different potency and duration, hydrocortisone and dexamethasone, into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with the goal to modulate inflammatory gene expression in a delivery-dependent manner. We evaluated their anti-inflammatory properties in two in vitro models varying the timing of treatment administration based on lipopolysaccharide M1-polarized macrophages, key effectors of the innate immune system. Our results demonstrated that, for both strategies, drug-loaded nanoparticles significantly reduced the expression of interleukin-6, a pro-inflammatory cytokine, compared to the free drugs. However, in one of the strategies, while free drugs induced upregulation of interleukin-10, a key anti-inflammatory cytokine, no such effect was observed with the nanoparticle-based formulations. Overall, these results demonstrate that PLGA nanoparticles enable sustained glucocorticoid delivery and modulate inflammatory gene expression in activated macrophages in a delivery- and timing-dependent manner, providing comparative insight into how glucocorticoid delivery via PLGA nanoparticles shapes inflammatory gene regulation depending on treatment timing and highlighting the importance of in vitro model design. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/DGA/E15-20R info:eu-repo/grantAgreement/EC/HORIZON EUROPE/101064735/EU/Tunning the force for remote magnetomechanical gating of Piezo1 channels/MAGPIEZ info:eu-repo/grantAgreement/ES/ISCIII/CB16-01/00263 info:eu-repo/grantAgreement/ES/MICINN/CEX2023-001286-S info:eu-repo/grantAgreement/ES/MICINN/PID2020-118485RB-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2022-141276OB-I00 info:eu-repo/semantics/openAccess by-nc https://creativecommons.org/licenses/by-nc/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Del Sol-Fernández, Susel Martín-Rapún, Rafael Universidad de Zaragoza (orcid)0000-0003-0702-8260 Martínez de la Fuente, Jesús (orcid)0000-0003-1081-8482 2013 765 Universidad de Zaragoza Dpto. Química Orgánica Área Química Orgánica (2026), [10 pp.] Nanoscale Horizons Nanoscale Horizons 2055-6756 2790944 http://zaguan.unizar.es/record/170172/files/texto_completo.pdf Versión publicada 2868993 http://zaguan.unizar.es/record/170172/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:170172 articulos driver 2026-03-26-14:31:00 ARTICLE