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

Abstract

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.

Robust, Reproducible Silica Scaffold for Liquid Flow Applications

“…Meso- and macroporous , siliceous materials have been studied extensively for use in diverse applications for over 20 years. They show promise in areas as diverse as heterogeneous catalysis, , energy storage, adsorption and separations, − and biomedical devices. − These siliceous materials are synthesized in a wide range of morphologies and by several processes to meet the diverse physical and chemical requirements of these applications. Common materials include composites, − ,, aerogels and xerogels, ,,, films and membranes, , particles, and microstructured monoliths. ,− Preparation methods include sol–gel processing, ,, templating methods, ,,,,, deposition, and a variety of other techniques.…”

Activity and Stability of Nanoconfined Alpha-Amylase in Mesoporous Silica

“…Mesoporous silica particles (MSPs) such as SBA-15 are characterized by a large surface area, variable mesopore size (2–50 nm), pore volume, mesocrystalline order, and ease of functionalization. , These properties can be fine-tuned and are attractive for controlling molecular diffusion. The hydrodynamic dimensions of enzymes can be in the order of the pore size of MSPs, and nonobvious and diffusion-related effects may be expected. , In addition to these features of diffusion and molecular control, this type of silica is researched for use in drug delivery, biocatalysis, and as therapeutic agents. – Recent research has also explored the potential of MSPs for therapeutic application and large-scale production. , …”

“…5−8 Recent research has also explored the potential of MSPs for therapeutic application and large-scale production. 9,10 Metabolic syndrome, which includes obesity and type 2 diabetes (T2D), is researched for its potential to be treated and prevented with MSPs. It was shown that amylase and lipase are adsorbed on MSPs in a pore-size-dependent manner both in vitro and ex vivo in gastric fluids.…”

“…11,13 Furthermore, it has been shown that MSPs pass through the gastrointestinal tract (GIT) of humans and mice without losing their structure and function. 10 The apparent reduced activity of enzymes has been attributed to the sizespecific adsorption of the enzymes (amylase and lipase) from complex gastric fluids and studied in vitro, ex vivo, and in vivo. 14,15 The digestive enzyme α-amylase belongs to the glycoside hydrolase family and cleaves glucan links in polysaccharides, such as starch and glycogen.…”

“…It was shown that amylase and lipase are adsorbed on MSPs in a pore-size-dependent manner both in vitro and ex vivo in gastric fluids. The pore-size dependency of the adsorption on MSPs is well-known, , and it has been demonstrated that MSPs can act as a molecular sieve for proteins. , Furthermore, it has been shown that MSPs pass through the gastrointestinal tract (GIT) of humans and mice without losing their structure and function . The apparent reduced activity of enzymes has been attributed to the size-specific adsorption of the enzymes (amylase and lipase) from complex gastric fluids and studied in vitro, ex vivo, and in vivo. , …”