Antioxidant properties of probucol released from mesoporous silica

Lau, Michael; Giri, Kalpeshkumar; Garcia‐Bennett, Alfonso E.

doi:10.1016/j.ejps.2019.105038

Cited by 11 publications

(11 citation statements)

References 51 publications

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“…The lack of a crystalline endotherm in the DSC traces or diffraction peaks in the high-angle XRD of loaded samples was evidence that the drug was loaded in an amorphous state (Figure 1b,c) [68]. As reported previously, drug loadings of PB higher than 30 wt.% led to the complete filling of the mesopore volume of AMS-6 and re-crystallization of the drug in the exterior of the particles [69]. To avoid this, samples with loading amounts of 29.5 wt.% AMS-6PB were prepared and used for cellular studies.…”

Section: Drug Loading and Dissolution Kineticssupporting

confidence: 73%

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

et al. 2022

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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.

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Section: Drug Loading and Dissolution Kineticssupporting

confidence: 73%

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

et al. 2022

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“…Additionally, the structure of bulk and confined PRO was examined using X-ray diffraction (XRD). This type of investigations seems to be important considering previous report demonstrating the enhancement in dissolution rate and antioxidant properties of PRO confined in mesoporous silica with respect to the bulk crystalline material . It is also worth stressing that recent studies have indicated that this API is characterized by an extremely high (one of the highest reported to date) pressure coefficient of the glass transition temperature, d T g /d p = 427 K/GPa, which quantifies the sensitivity of the structural relaxation dynamics to the density fluctuation.…”

Section: Introductionmentioning

confidence: 72%

“…This type of investigations seems to be important considering previous report demonstrating the enhancement in dissolution rate and antioxidant properties of PRO confined in mesoporous silica with respect to the bulk crystalline material. 48 It is also worth stressing that recent studies have indicated that this API is characterized by an extremely high (one of the highest reported to date) pressure coefficient of the glass transition temperature, dT g /dp = 427 K/GPa, 49 which quantifies the sensitivity of the structural relaxation dynamics to the density fluctuation. Therefore, it seems to be a perfect candidate to probe the impact of surface interactions with pore walls on the molecular mobility for the samples confined into porous templates.…”

Section: Introductionmentioning

confidence: 99%

Anormal Thermal History Effect on the Structural Dynamics of Probucol Infiltrated into Porous Alumina

et al. 2021

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Herein, broadband dielectric (BDS) and Fourier transform infrared spectroscopy (FTIR), together with differential scanning calorimetry (DSC) and X-ray diffraction (XRD), were applied to study the molecular dynamics, molecular interactions as well as physical stability of an amorphous Active Pharmaceutical Ingredient (API) probucol (PRO)infiltrated into anodic aluminum oxide (AAO) membranes of pore size, d ∼ 10−160 nm. Interestingly, the behavior of examined substance strongly depends on the applied thermal protocol. Remarkably, for the first time, we observed that the structural dynamics of the slowly cooled PRO under confinement is significantly enhanced when compared to that of the quenched material. This unusual behavior was interpreted as a result of surface-induced effects (including the formation of well-resolved interfacial H-bonded layer and adsorption− desorption processes near the interface) that are magnified by the extremely high sensitivity to density fluctuation of studied PRO, reflected in the enormous pressure coefficient of the glass transition temperature dT g /dp = 427 K/GPa. In fact, FTIR investigations revealed that PRO tends to self-associate under confinement and forms a strongly bonded interfacial layer, which controls the variation in the structural dynamics of core molecules. Finally, we observed that the tendency to crystallize of confined API is reduced with respect to the bulk, even though the critical size of PRO nuclei (r c ∼ 3 nm) is significantly lower than the smallest examined pore size. Nevertheless, after few weeks of storage, the investigated substance crystallized in larger pores, while it remained stable in the nanochannels of d = 10 nm. A combination of XRD and DSC measurements indicated that the infiltrated PRO forms two polymorphs, the stable form I (dominating in bulk) and unstable form II (prevailing under confinement). That means that porous matrices might be used to obtain and maintain prolonged stability of unstable polymorphic forms of API.

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“…Currently, they can be used as adjunct drugs in combination with conventional glaucoma drugs to improve patient outcomes. Another important thing to consider when using antioxidants is that effective antioxidants are often hydrophobic and less water-soluble [115] . Therefore, it is important to take necessary measures to improve drug availability for improving drug efficacy.…”

Section: Mitochondrial Dysfunction In Glaucomamentioning

confidence: 99%

Mitochondrial dysfunction in glaucomatous degeneration

Zhang¹,

Chen²,

Zhang³

2023

Int J Ophthalmol

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Glaucoma is a kind of optic neuropathy mainly manifested in the permanent death of retinal ganglion cells (RGCs), atrophy of the optic nerve, and loss of visual ability. The main risk factors for glaucoma consist of the pathological elevation of intraocular pressure (IOP) and aging. Although the mechanism of glaucoma remains an open question, a theory related to mitochondrial dysfunction has been emerging in the last decade. Reactive oxygen species (ROS) from the mitochondrial respiratory chain are abnormally produced as a result of mitochondrial dysfunction. Oxidative stress takes place when the cellular antioxidant system fails to remove excessive ROS promptly. Meanwhile, more and more studies show that there are other common features of mitochondrial dysfunction in glaucoma, including damage of mitochondrial DNA (mtDNA), defective mitochondrial quality control, ATP reduction, and other cellular changes, which are worth summarizing and further exploring. The purpose of this review is to explore mitochondrial dysfunction in the mechanism of glaucomatous optic neuropathy. Based on the mechanism, the existing therapeutic options are summarized, including medications, gene therapy, and red-light therapy, which are promising to provide feasible neuroprotective ideas for the treatment of glaucoma.

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Antioxidant properties of probucol released from mesoporous silica

Cited by 11 publications

References 51 publications

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

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

Anormal Thermal History Effect on the Structural Dynamics of Probucol Infiltrated into Porous Alumina

Mitochondrial dysfunction in glaucomatous degeneration

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