Entrapping Digestive Enzymes with Engineered Mesoporous Silica Particles Reduces Metabolic Risk Factors in Humans

Waara, Erik Rollman; Iqbal, Muhammad N.; Robert‐Nicoud, Ghislaine; Benziane, Boubacar; Vallhov, Helen; Wasik, Agata M.; Lindgren, Maria; Hagman, Emilia; Rinde, Mia; Kupferschmidt, Natalia; Berlin, Roger; Johnston, Eric V.; Danielsson, Pernilla; Bengtsson, Tore

doi:10.1002/adhm.202000057

Cited by 8 publications

(35 citation statements)

References 47 publications

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“… The presence of micropores is hypothesized to disrupt the native structure of the esterase enzyme through conformation changes, hence, resulting in reduction of its hydrolytic activity. Previous studies have documented that the adsorption of digestive enzyme into the pores of MPS causes changes in activity due to the influence of the silica curvature on enzyme immobilization. − However, further studies are required to systematically investigate the impact of micropores on esterase activity. …”

Section: Resultsmentioning

confidence: 99%

Role of Silica Intrawall Microporosity on Abiraterone Acetate Solubilization and In Vivo Oral Absorption

et al. 2022

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SBA-15 mesoporous silica (MPS) has been widely used in oral drug delivery; however, it has not been utilized for solidifying lipid-based formulations, and the impact of their characteristic intrawall microporosity remains largely unexplored. Here, we derive the impact of the MPS microporosity on the in vitro solubilization and in vivo oral pharmacokinetics of the prostate cancer drug abiraterone acetate (AbA) when coencapsulated along with medium chain lipids into the pores. AbA in lipid (at 80% equilibrium solubility) was imbibed within a range of MPS particles (with comparable morphology and mesoporous structure but contrasting microporosity ranging from 0−247 m 2 /g), and their solid-state properties were characterized. Drug solubilization studies during in vitro lipolysis revealed that microporosity was the key factor in facilitating AbA solubilization by increasing the surface area available for drug−lipid diffusion. Interestingly, microporosity hindered hydrolysis of AbA to its active metabolite, abiraterone (Ab), under simulated intestinal conditions. This unique relationship between microporosity and AbA/Ab aqueous solubilization behavior was hypothesized to have significant implications on the subsequent bioavailability of the active metabolite. In vivo oral pharmacokinetics studies in male Sprague−Dawley rats revealed that MPS with moderate microporosity attained the highest relative bioavailability, while poor in vitro−in vivo correlations (IVIVC) existed between in vitro drug solubilization during lipolysis and in vivo AUC. Despite this, a reasonable IVIVC was established between the in vitro solubilization and in vivo C max , providing evidence for an association between silica microporosity and oral drug absorption.

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Section: Resultsmentioning

confidence: 99%

Role of Silica Intrawall Microporosity on Abiraterone Acetate Solubilization and In Vivo Oral Absorption

et al. 2022

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“…Our results agree with previous studies that demonstrated hypocholesterolemic properties of silicon from many different sources such as silicon dioxide, [ 21 ] nanostructure aluminosilicate compounds, [ 30 ] silicon‐enriched spirulina, [ 31 ] or mesoporous silica. [ 32 ] Some of them even link the hypocholesteromic effect with the reduction of cholesterol absorption, [ 21,30,32 ] although none delve into the molecular mechanisms involved.…”

Section: Discussionmentioning

confidence: 99%

Could Duodenal Molecular Mechanisms be Involved in the Hypocholesterolemic Effect of Silicon Used as Functional Ingredient in Late‐Stage Type 2 Diabetes Mellitus?

Hernández-Martín

Bocanegra

Redondo-Castillejo

et al. 2022

Molecular Nutrition Food Res

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Scope: Hypercholesterolemia increases the risk of mortality in type 2 diabetes mellitus (T2DM), especially in the late-stage. Consumption of bioactive compounds as functional ingredients would help achieve therapeutic goals for cholesterolemia. Silicon has demonstrated a hypocholesterolemic effect and the ability to reduce fat digestion. However, it is unclear whether silicon exerts such effect in late-stage T2DM (LD) and the intestinal mechanisms involved. Methods and results: Three groups of eight rats were included: early-stage T2DM control (ED), LD, and the LD group treated with silicon (LD-Si) once the rats were diabetic. Morphological alterations of the duodenal mucosa, and levels of markers involve in cholesterol absorption and excretion, beside cholesterolemia, and fecal excretion were assayed. Silicon included as a functional ingredient significantly reduces cholesterolemia in part due to: 1) reducing cholesterol intestinal absorption by decreasing the absorptive area and Acetyl-Coenzyme A acetyltransferase-2 (ACAT2) levels; and 2) increasing cholesterol excretion to the lumen by induction of the liver X receptor (LXR) and consequent increase of adenosine triphosphate-binding cassette transporter (ABCG5/8). Conclusions: These results provide insight into the intestinal molecular mechanisms by which silicon reduces cholesterolemia and highlights the efficacy of the consumption of silicon-enriched functional foods in late-stage T2DM.

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“…In line with this effect, we hypothesized that amylase and lipase were adsorbed in the particles and further interactions with substrates were hindered. 2 As the internal specific surface area exceeds significantly the external one, surface interactions inside the pores have an auxiliary effect. 46−49 Physical separation and molecular retention in the pores protect particles from gastrointestinal (GI) fluids and physio-chemical disintegration.…”

Section: Extraction and Subsequent Calcination Of Msps From Murine An...mentioning

confidence: 99%

“…In contrast, bigger pores were found to be occupied by organic matter which we attribute to the adsorption of GIT biomolecules such as α-amylase, in line with our previous findings. 2 It was notable that the acid-extracted and calcined MSPs had a higher capacity for α-amylase adsorption (2−3 times) than pristine MSPs. Higher K values (in the Hill model) were observed for MSP 2 than that for MSP 1 which had slightly smaller pores.…”

Section: Extraction and Subsequent Calcination Of Msps From Murine An...mentioning

confidence: 99%

“…Mesoporous silica particles (MSPs) have pores of 2–50 nm and are researched for applications that include food science, therapeutics, and drug delivery. − Ordered MSPs have tunable physical characteristics such as surface area, pore volume, pore size, morphology, crystallography, and particle size. The archetypical ones are those of the Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM) types. , Their high internal surface areas and pore volumes also imply that they can circumvent the often-slow pharmacokinetics for oral formulations. − These features give MSPs the ability to rapidly transport mass; for example, it is reported that the transport of ibuprofen through MSPs is very fast (with a mass transport coefficient of 1 × 10 –4 s –1 ) .…”

Section: Introductionmentioning

confidence: 99%

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Mesoporous Silica Particles Retain Their Structure and Function while Passing through the Gastrointestinal Tracts of Mice and Humans

Iqbal

Robert‐Nicoud

Ciurans-Oset

et al. 2023

ACS Appl. Mater. Interfaces

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Mesoporous silica particles (MSPs) can be used as food additives, clinically for therapeutic applications, or as oral delivery vehicles. It has also been discussed to be used for a number of novel applications including treatment for diabetes and obesity. However, a major question for their possible usage has been if these particles persist structurally and retain their effect when passing through the gastrointestinal tract (GIT). A substantial breaking down of the particles could reduce function and be clinically problematic for safety issues. Hence, we investigated the biostability of MSPs of the SBA-15 kind prepared at large scales (100 and 1000 L). The MSPs were orally administered in a murine model and clinically in humans. A joint extraction and calcination method was developed to recover the MSPs from fecal mass, and the MSPs were characterized physically, structurally, morphologically, and functionally before and after GIT passage. Analyses with N2 adsorption, X-ray diffraction, electron microscopy, and as a proxy for general function, adsorption of the enzyme α-amylase, were conducted. The adsorption capacity of α-amylase on extracted MSPs was not reduced as compared to the pristine and control MSPs, and adsorption of up to 17% (w/w) was measured. It was demonstrated that the particles did not break down to any substantial degree and retained their function after passing through the GITs of the murine model and in humans. The fact the particles were not absorbed into the body was ascribed to that they were micron-sized and ingested as agglomerates and too big to pass the intestinal barrier. The results strongly suggest that orally ingested MSPs can be used for a number of clinical applications.

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Entrapping Digestive Enzymes with Engineered Mesoporous Silica Particles Reduces Metabolic Risk Factors in Humans

Cited by 8 publications

References 47 publications

Role of Silica Intrawall Microporosity on Abiraterone Acetate Solubilization and In Vivo Oral Absorption

Role of Silica Intrawall Microporosity on Abiraterone Acetate Solubilization and In Vivo Oral Absorption

Could Duodenal Molecular Mechanisms be Involved in the Hypocholesterolemic Effect of Silicon Used as Functional Ingredient in Late‐Stage Type 2 Diabetes Mellitus?

Mesoporous Silica Particles Retain Their Structure and Function while Passing through the Gastrointestinal Tracts of Mice and Humans

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