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

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 144; pp. 132 - 138
• Main Authors: Kamakura, Remi, Kovalainen, Miia, Riikonen, Joakim, Nissinen, Tuomo, Shere Raza, Ghulam, Walkowiak, Jaroslaw, Lehto, Vesa-Pekka, Herzig, Karl-Heinz
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2019
• Subjects: Controlled delivery; Enteroendocrine cells; Food intake; GLP-1; Nutrients; Porous silicon; α-linolenic acid; Controlled delivery; GLP-1; Food intake; α-linolenic acid; Nutrients; Porous silicon; Enteroendocrine cells
• ISSN: 0939-6411; 1873-3441; 1873-3441
• DOI: 10.1016/j.ejpb.2019.09.009

[Display omitted] 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. α-Linolenic acid (αLA) 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 αLA to increase secretion of gastrointestinal peptides. αLA was loaded to thermally hydrocarbonized porous silicon particles (THCPSi). 47.9 ± 3.84% and 30.7 ± 2.86% of αLA was released during 6 h from 3.0% and 9.2% loading degree (w/w) samples in vitro, respectively. Native αLA (50 µM) significantly increased GLP-1 secretion from enteroendocrine STC-1 and GLUTag cell lines. αLA 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 αLA, increasing GLP-1 secretion. Our results justify further in vivo investigations.