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To address this, we developed polymeric nanoparticles (NPs), using poly(lactic\u2010co\u2010glycolic acid) (PLGA), encapsulating CBD using nanoprecipitation, aiming to create an effective CBD\u2010nanoformulation for metabolic disorder treatment. These NPs (135\u2013265\u2009nm) demonstrated high encapsulation efficiency (EE%\u2009\u2248\u2009100%) and sustained release kinetics. Their therapeutic potential was evaluated in an in\u00a0vitro metabolic syndrome model employing sodium palmitate\u2010induced HepG2 cells. Key assessment parameters included cell viability (MTT assay), glucose uptake, lipid accumulation (Oil Red O staining), triglycerides, cholesterol, HDL\u2010c levels, and gene expression of metabolic regulators. Results showed an IC50 of 9.85\u2009\u03bcg\/mL for free CBD and 11.26\u2009\u03bcg\/mL for CBD\u2010loaded NPs. CBD\u2010loaded NPs significantly enhanced glucose uptake, reduced lipid content, lowered triglycerides and total cholesterol, and increased HDL\u2010c levels compared to free CBD. Gene analysis indicated reduced gluconeogenesis via downregulation of PPAR\u03b3, FOXO\u20101, PEPCK, and G6Pase and enhanced fatty acid oxidation through CPT\u20101 upregulation. These findings suggest that CBD\u2010loaded NPs may serve as a novel therapeutic strategy for the management of metabolic disorders, warranting further in\u00a0vivo studies.<\/jats:p>","DOI":"10.1002\/jbm.a.37916","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T13:49:41Z","timestamp":1745588981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enhanced Metabolic Syndrome Management Through Cannabidiol\u2010Loaded <scp>PLGA<\/scp> Nanoparticles: Development and In\u00a0Vitro Evaluation"],"prefix":"10.1002","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3563-5159","authenticated-orcid":false,"given":"Mazen M.","family":"El\u2010Hammadi","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Mart\u00edn\u2010Navarro","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Berrocoso","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Salud Mental (CIBERSAM)  Madrid Spain"},{"name":"Neuropsychopharmacology &amp; Psychobiology Research Group, Department of Psychology University of Cadiz  C\u00e1diz Spain"},{"name":"Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA) Research Unit Puerta del Mar University Hospital, University of C\u00e1diz  C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefa","family":"\u00c1lvarez\u2010Fuentes","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy Universidad de Sevilla  Sevilla Spain"},{"name":"Instituto de Biomedicina de Sevilla (IBIS)\u2010Campus Hospital Universitario Virgen del Roc\u00edo  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedicto","family":"Crespo\u2010Facorro","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Salud Mental (CIBERSAM)  Madrid Spain"},{"name":"Instituto de Biomedicina de Sevilla (IBIS)\u2010Campus Hospital Universitario Virgen del Roc\u00edo  Sevilla Spain"},{"name":"Department of Psychiatry School of Medicine, University Hospital Virgen del Rocio  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Su\u00e1rez\u2010Pereira","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Salud Mental (CIBERSAM)  Madrid Spain"},{"name":"Biomedical Research and Innovation Institute of C\u00e1diz (INiBICA) Research Unit Puerta del Mar University Hospital, University of C\u00e1diz  C\u00e1diz Spain"},{"name":"Neuropsychopharmacology &amp; Psychobiology Research Group, Department of Neuroscience University of Cadiz  C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"V\u00e1zquez\u2010Bourgon","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Salud Mental (CIBERSAM)  Madrid Spain"},{"name":"Department of Psychiatry University Hospital Marqu\u00e9s de Valdecilla. 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