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

Abstract

Mesoporous silica particles (MSPs) are emerging as an interesting option to reduce calorific uptake as a treatment for obesity and other metabolic conditions. However, their further development under the pharmaceutical regulatory framework is hindered by poor understanding of the mechanisms by which they exert their effects. In the current study the interaction of MSPs with the lipid digestion process is investigated, specifically interactions with lipase enzymes and lipid digestion products as a key contributing factor to lipid absorption and calorific intake. The impact of exposing lipase to MSPs on the enzyme activity was assessed directly using the tributyrin digestion test. The extent of interaction of digestion products with MSPs was studied using selectively radiolabeled bile components and lipids, while the impact on in vivo absorption of lipids was studied by incorporation of radiolabelled lipid (triolein) into milk and administration with and without particles. The studies showed that particles that inhibited lipase activity also tended to interact more extensively with lipid digestion products. In vitro X-ray scattering studies revealed the interaction of some MSPs with lipid digestion products through changes in lipid self-assembly during digestion. The MSPs led to reduced lipid absorption in vivo compared to the control particles and MSP-free milk. While the specific properties of the MSPs that drive the differences between the behavior of MSPs during lipid digestion remain elusive, the studies highlight that interactions with the lipid digestion and absorption pathways are a likely mechanism for reducing calorific uptake.