{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:49:02Z","timestamp":1791254942656,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["IC210100040"],"award-info":[{"award-number":["IC210100040"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["IC210100040"],"award-info":[{"award-number":["IC210100040"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT150100342"],"award-info":[{"award-number":["FT150100342"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Brain endothelial cells mediate the function and integrity of the blood brain barrier (BBB) by restricting its permeability and exposure to potential toxins. However, these cells are highly susceptible to cellular damage caused by oxidative stress and inflammation. Consequent disruption to the integrity of the BBB can lead to the pathogenesis of neurodegenerative diseases. Drug compounds with antioxidant and\/or anti-inflammatory properties therefore have the potential to preserve the structure and function of the BBB. In this work, we demonstrate the enhanced antioxidative effects of the compound probucol when loaded within mesoporous silica particles (MSP) in vitro and in vivo zebrafish models. The dissolution kinetics were significantly enhanced when released from MSPs. An increased reduction in lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), cyclooxygenase (COX) enzyme activity and prostaglandin E2 production was measured in human brain endothelial cells treated with probucol-loaded MSPs. Furthermore, the LPS-induced permeability across an endothelial cell monolayer by paracellular and transcytotic mechanisms was also reduced at lower concentrations compared to the antioxidant ascorbic acid. Zebrafish pre-treated with probucol-loaded MSPs reduced hydrogen peroxide-induced ROS to control levels after 24-h incubation, at significantly lower concentrations than ascorbic acid. We provide compelling evidence that the encapsulation of antioxidant and anti-inflammatory compounds within MSPs can enhance their release, enhance their antioxidant effects properties, and open new avenues for the accelerated suppression of neuroinflammation.<\/jats:p>","DOI":"10.3390\/pharmaceutics14030502","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T21:11:07Z","timestamp":1645737067000},"page":"502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Enhanced Antioxidant Effects of the Anti-Inflammatory Compound Probucol When Released from Mesoporous Silica Particles"],"prefix":"10.3390","volume":"14","author":[{"given":"Michael","family":"Lau","sequence":"first","affiliation":[{"name":"School of Natural Sciences, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Sealy","sequence":"additional","affiliation":[{"name":"Malaria and Microvesicles Research Group, School of Life Science, Faculty of Science, University of Technology Sydney, Ultimo, Sydney, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Combes","sequence":"additional","affiliation":[{"name":"Malaria and Microvesicles Research Group, School of Life Science, Faculty of Science, University of Technology Sydney, Ultimo, Sydney, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9484-8050","authenticated-orcid":false,"given":"Marco","family":"Morsch","sequence":"additional","affiliation":[{"name":"Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-0179","authenticated-orcid":false,"given":"Alfonso E.","family":"Garcia-Bennett","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Macquarie University, Sydney, NSW 2109, Australia"},{"name":"Australian Research Council Industrial Transformation Training Centre for Facilitated Advancement of Australia\u2019s Bioactives (FAAB), Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s00281-009-0177-0","article-title":"The blood\u2013brain and the blood\u2013cerebrospinal fluid barriers: Function and dysfunction","volume":"31","author":"Engelhardt","year":"2009","journal-title":"Semin. 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