Towards mesoporous silica as a pharmaceutical treatment for obesity - impact on lipid digestion and absorption

May, Kellie L.; Pham, Anna C.; Ramirez, Gisela; Herrera-Hidalgo, Carmen; Iqbal, Muhammad N.; Robert‐Nicoud, Ghislaine; Clulow, Andrew J.; Bengtsson, Tore; Boyd, Ben J.

doi:10.1016/j.ejpb.2022.02.001

Cited by 6 publications

(8 citation statements)

References 24 publications

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“…It is responsible for the release of maltose, etc. It has been shown that the activity of α-amylase from a variety of sources is drastically reduced when adsorbed on MSPs. ,, Similar findings have been observed for other enzymes when adsorbed on MSPs. – The reduction of enzymatic activity in the presence of MSPs can be of significance for the use of MSPs in drug administration and therapeutic and biocatalytic applications. This reduction could relate to the deactivation of the enzyme on adsorption, minor conformational changes, or complete loss of the secondary and tertiary structures that enzymes need to maintain for their function. – However, the observed reduced activity could also relate to a substrate that is too large to fit the pores of the MSPs where the enzymes are presorbed .…”

Section: Introductionsupporting

confidence: 55%

“… 13 , 16 , 17 Similar findings have been observed for other enzymes when adsorbed on MSPs. 18 – 21 The reduction of enzymatic activity in the presence of MSPs can be of significance for the use of MSPs in drug administration and therapeutic and biocatalytic applications. This reduction could relate to the deactivation of the enzyme on adsorption, minor conformational changes, or complete loss of the secondary and tertiary structures that enzymes need to maintain for their function.…”

Section: Introductionmentioning

confidence: 99%

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Activity and Stability of Nanoconfined Alpha-Amylase in Mesoporous Silica

et al. 2023

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Mesoporous silica particles (MSPs) have been studied for their potential therapeutic uses in controlling obesity and diabetes. Previous studies have shown that the level of digestion of starch by α-amylase is considerably reduced in the presence of MSPs, and it has been shown to be caused by the adsorption of α-amylase by MSPs. In this study, we tested a hypothesis of enzymatic deactivation and measured the activity of α-amylase together with MSPs (SBA-15) using comparably small CNP-G3 (2-chloro-4-nitrophenyl alpha-d-maltotrioside) as a substrate. We showed that pore-incorporated α-amylase was active and displayed higher activity and stability compared to amylase in solution (the control). We attribute this to physical effects: the coadsorption of CNP-G3 on the MSPs and the relatively snug fit of the amylase in the pores. Biosorption in this article refers to the process of removal or adsorption of α-amylase from its solution phase into the same solution dispersed in, or adsorbed on, the MSPs. Large quantities of α-amylase were biosorbed (about 21% w/w) on the MSPs, and high values of the maximum reaction rate (V max) and the Michaelis–Menten constant (K M) were observed for the enzyme kinetics. These findings show that the reduced enzymatic activity for α-amylase on MSP observed here and in earlier studies was related to the large probe (starch) being too large to adsorb in the pores, and potato starch has indeed a hydrodynamic diameter much larger than the pore sizes of MSPs. Further insights into the interactions and environments of the α-amylase inside the MSPs were provided by 1H fast magic-angle spinning (MAS) nuclear magnetic resonance (NMR) and 13C/15N dynamic nuclear polarization MAS NMR experiments. It could be concluded that the overall fold and solvation of the α-amylase inside the MSPs were nearly identical to those in solution.

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Section: Introductionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Activity and Stability of Nanoconfined Alpha-Amylase in Mesoporous Silica

et al. 2023

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“…In addition, in the C57Bl/6 mice diet-induced obesity model, mesoporous silica particles supplemented in food successfully reduced adipose tissue formation (6.5 ± 0.5 vs. 9.4 ± 1.2 g), leptin levels (32.8 ± 7.4 vs. 16.9 ± 1.9 ng/mL), and 33% reduction of food efficiency in comparison to mice in the control group [ 32 ]. More importantly, based on the influence on lipid levels and lipid digestion products, mesoporous silica particles are emerging as an interesting option to act as a treatment for obesity and other metabolic conditions [ 33 ]. Similarly, in our study, we found that PMS could reduce LDL-C levels in the plasma in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Firstly, PMS-HP acted as a solid-phase extraction material to adsorb LDL-C, resulting in a reduction in LDL-C. As was shown in our study, LDL-C adsorbed by PMS-HP could be released with a high-concentration sodium chloride solution, proving the fact that PMS-HP could adsorb LDL-C through physical sequestration. Secondly, the formation of PMS-HP-LDL-C complexes resulted in a disruption of the normal interaction between blood lipids and lipase, resulting in impaired lipase activity [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Functionalized Periodic Mesoporous Silica Nanoparticles for Inhibiting the Progression of Atherosclerosis by Targeting Low-Density Lipoprotein Cholesterol

Jin,

Lu,

Zhang

et al. 2024

Pharmaceutics

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Atherosclerotic disease is a substantial global burden, and existing treatments, such as statins, are recommended to lower low-density lipoprotein cholesterol (LDL-C) levels and inhibit the progression of atherosclerosis. However, side effects, including gastrointestinal unease, potential harm to the liver, and discomfort in the muscles, might be observed. In this study, we propose a novel method using periodic mesoporous silica nanoparticles (PMS) to create heparin-modified PMS (PMS-HP) with excellent biocompatibility, enabling selective removal of LDL-C from the blood. In vitro, through the introduction of PMS-HP into the plasma of mice, we observed that, compared to PMS alone, PMS-HP could selectively adsorb LDL-C while avoiding interference with valuable components such as plasma proteins and high-density lipoprotein cholesterol (HDL-C). Notably, further investigations revealed that the adsorption of LDL-C by PMS-HP could be well-fitted to quasi-first-order (R2 = 0.993) and quasi-second-order adsorption models (R2 = 0.998). Likewise, in vivo, intravenous injection of PMS-HP enabled targeted LDL-C adsorption (6.5 ± 0.73 vs. 8.6 ± 0.76 mM, p < 0.001) without affecting other plasma constituents, contributing to reducing intravascular plaque formation (3.66% ± 1.06% vs. 1.87% ± 0.79%, p < 0.05) on the aortic wall and inhibiting vascular remodeling (27.2% ± 6.55% vs. 38.3% ± 1.99%, p < 0.05). Compared to existing lipid adsorption techniques, PMS-HP exhibited superior biocompatibility and recyclability, rendering it valuable for both in vivo and in vitro applications.

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“…Porous silica is one such colloid that has received increasing attention for its antiobesity potential, with oral dosing triggering reductions in metabolic risk factors in both animal obesity models [9,14,15] and human clinical studies [11,16]. Importantly, in a Phase I human clinical study, it was shown that oral dosing of porous silica did not trigger any abdominal discomfort, with minimal and inconsistent changes in bowel habits reported, compared to a placebo control [17], thus highlighting the safety and tolerability of this as an anti-obesity therapy, which is a fundamental consideration given the GI complications associated with orlistat.…”

Section: Introductionmentioning

confidence: 99%

The Anti-Obesity Effect of Porous Silica Is Dependent on Pore Nanostructure, Particle Size, and Surface Chemistry in an In Vitro Digestion Model

Chen

Hanrahan²,

McGrath³

et al. 2022

Pharmaceutics

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The potential for porous silica to serve as an effective anti-obesity agent has received growing attention in recent years. However, neither the exact pharmacological mechanism nor the fundamental physicochemical properties of porous silica that drive its weight-lowering effect are well understood. Subsequently, in this study, an advanced in vitro digestion model capable of monitoring lipid and carbohydrate digestion was employed to elucidate the effect of porous silica supplementation on digestive enzyme activities. A suite of porous silica samples with contrasting physicochemical properties was investigated, where it was established that the inhibitory action of porous silica on digestive enzyme functionality was strongly dependent on porous nanostructure, particle size and morphology, and surface chemistry. Insights derived from this study validate the capacity of porous silica to impede the digestive processes mediated by pancreatic lipase and α-amylase within the gastrointestinal tract, while the subtle interplay between porous nanostructure and enzyme inhibition indicates that the anti-obesity effect can be optimized through strategic particle design.

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Towards mesoporous silica as a pharmaceutical treatment for obesity - impact on lipid digestion and absorption

Cited by 6 publications

References 24 publications

Activity and Stability of Nanoconfined Alpha-Amylase in Mesoporous Silica

Activity and Stability of Nanoconfined Alpha-Amylase in Mesoporous Silica

Functionalized Periodic Mesoporous Silica Nanoparticles for Inhibiting the Progression of Atherosclerosis by Targeting Low-Density Lipoprotein Cholesterol

The Anti-Obesity Effect of Porous Silica Is Dependent on Pore Nanostructure, Particle Size, and Surface Chemistry in an In Vitro Digestion Model

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