Inorganic mesoporous particles for controlled α-linolenic acid delivery to stimulate GLP-1 secretion in vitro

Novel treatment methods for obesity are urgently needed due to the increasing global severity of the problem. Gastrointestinal hormones, such as GLP-1 and PYY, are secreted by the enteroendocrine cells, playing a critical role in regulating food intake. Digested nutrients trigger the secretion of these hormones, which have a very short half-life. alpha-Linolenic acid (alpha LA) has been shown to stimulate GLP-1 secretion, however, chemical instability and fast uptake in the small intestine hinder its use in body weight management. We developed a novel delivery system based on inorganic mesoporous particles for alpha LA to increase secretion of gastrointestinal peptides. alpha LA was loaded to thermally hydrocarbonized porous silicon particles (THCPSi). 47.9 +/- 3.84% and 30.7 +/- 2.86% of alpha LA was released during 6 h from 3.0% and 9.2% loading degree (w/w) samples in vitro, respectively. Native alpha LA (50 mu M) significantly increased GLP-1 secretion from enteroendocrine STC-1 and GLUTag cell lines. alpha LA loaded THCPSi significantly and dose dependently stimulated GLP-1 secretion from STC-1 cells, whereas empty particles did not. We demonstrated in vitro that THCPSi particles have the potential to be used as a controlled delivery system for nutrients such as alpha LA, increasing GLP-1 secretion. Our results justify further in vivo investigations.