Effect of starch molecular weight on the colon-targeting delivery and promoting GLP-1 secretion of starch-lecithin complex nanoparticles

β-lactoglobulin (β-LG) could stimulate enteroendocrine L cells which are located in the colon to secrete glucagon-like peptide-1 (GLP-1) to maintain glycemic homeostasis. In order to ensure that β-LG can intactly arrive in the colon through oral administration, colon-targeting delivery systems should be engineered. In this study, β-LG encapsulated nanoparticles were fabricated through molecular interaction and self-assembly using octenyl succinic anhydride (OSA) modified potato starch-lecithin complex (OPC) with different starch molecular weight (Mw). OPC with lower starch Mw exhibited stronger interaction with β-LG and its correspondent nanoparticles showed smaller diameter and higher structural compactness. Obtained OPC based nanoparticles were spherical, of Z-average diameter from 139.9 nm to 246.8 nm, of zeta-potential from -1.94 mV to -9.42 mV and of α value from 1.41 to 2.14. Additionally, OPC based nanoparticles with lower starch Mw exhibited excellent capacity for maintaining structure integrality in simulated upper gastrointestinal tract (GIT) environment. Optimized OPC based nanoparticles with 224.4 nm of diameter, -9.00 mV of zeta-potential and 2.14 of α value had well mucus-penetrating capacity (59.25%) and colon-targeting capacity (49.18% released in simulated colonic fluid). Moreover, the OPC based nanoparticles passed through the upper GIT signally stimulated GLP-1 secretion (improved 119.23%) primarily through β-LG targeting released in colon in the prophase and short-chain fatty acids and reducing sugar produced by colonic microbial degradation of OPC in the later phase. Altogether, OPC based nanoparticles have great potential of mucus penetrating and colon-targeting delivery systems for use in stimulating GLP-1 secretion which can support applications for maintaining glycemic homeostasis.