Enhanced bioaccessibility of cyclolinopeptides via zein-cyclodextrin nanoparticles: Simulated gastrointestinal digestion and cellular uptake study

Cyclolinopeptides (CLS) are hydrophobic cyclic peptides in flaxseed with multiple bioactive activities. This study developed zein ( Z )-cyclodextrin (CD) binary nanoparticles (NPs) as an oral delivery system for CLS. Z -CD NP had a smaller diameter (D h ) and better encapsulation effect on CLS. Formation of CLS-loaded NPs was driven by hydrogen bonds and electrostatic interactions. Presence of CD improved the thermal, pH and storage stabilities of NPs. Besides, CD prevented premature release of CLS in the stomach and enhanced the bioaccessibility of CLS to a maximum of 86.71 % ± 2.20 %. Lipid-raft-mediated endocytosis was involved in the cell uptake of NPs, where the addition of CD significantly facilitated the uptake of NPs. Z -CD NPs also enhanced absorption and reduced secretion of CLS after digestion. Overall, this study provides a simple approach to enhance the oral delivery efficiency of CLS by modulating Z-based NPs with CD.