Enhanced Antioxidant Effects of the Anti-Inflammatory Compound Probucol When Released from Mesoporous Silica Particles

Abstract

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.

Mesoporous Materials as Elements of Modern Drug Delivery Systems for Anti-Inflammatory Agents: A Review of Recent Achievements

“…Brain endothelial cells that provide the proper function and integrity of the blood brain barrier are highly susceptible to cellular damage caused by oxidative stress and inflammation. The group of Garcia-Bennet [ 164 ] observed the enhanced antioxidant effect of the anti-inflammatory compound probucol when released from mesoporous silica particles. The increased reduction of ROS, COX enzyme activity and PGE 2 production was measured in human brain endothelial cells treated with probucol-loaded mesoporous silica particles.…”

Reactivity of tert‐butylperoxyl radical with some phenylthiazolidine derivatives and probucol

“…Butylated hydroxytoluene (BHT) and probucol were used as reference AOs, the structure of which contains potentially antiradical sites, phenolic OH groups, and in the case of probucol, also a sulfide groups. 27,28 The reaction chemical mechanism of t-BuOO • with the compounds mentioned above is also examined. The anti-t-BuOO • reactivities with studied compounds is presented as two parameters: the absolute rate constants (k react ), which indicates kinetic antiradical/AO activity and AO free-radical capacities (f R ), the number of t-BuOO • destroyed by one molecule of AO.…”

“…This task was solved by direct kinetic measurements using EPR spectroscopy for the reactions of t ‐BuOO • with these compounds in lipophilic organic media. Butylated hydroxytoluene (BHT) and probucol were used as reference AOs, the structure of which contains potentially antiradical sites, phenolic OH groups, and in the case of probucol, also a sulfide groups 27,28 …”

Probucol will become a new model for treating cerebral infarction with a high risk of hemorrhage: A narrative review

“…Furthermore, PU has strong antiaging, restenosis prevention, and postoperative angioplasty treatment properties, which have piqued the interest of many clinicians in various professions. [ 11 12 13 14 15 16 ] PU is taken aback by the new appeal of this type of old medicine, which has faded from the Western market. Some heavyweight experts have written papers saying, “It is too early for us to give up!”[ 2 ] This review focuses on new clinical evidence and secondary prevention mechanisms for cerebrovascular diseases with a high risk of hemorrhage.…”