β-Glucan-Modified Liposomes for Microfold Cell-Targeted Oral Delivery of Food-Derived Angiotensin I-Converting Enzyme Inhibitory Peptides Using Microfluidics.

Abstract

This study presents a novel oral delivery system for food-derived angiotensin I-converting enzyme (ACE) inhibitory peptides by integrating β-glucan-functionalized liposomes with microfluidic encapsulation and receptor-mediated targeting. Two peptides, RADHPFL and YAEERYPIL derived from egg white proteins, were encapsulated into liposomes (composed of lecithin, cholesterol, and DSPE-β-glucan) via a controlled microfluidic self-assembly process. Encapsulation significantly improved the gastrointestinal stability of the peptides and preserved their ACE inhibitory activity compared to free peptides. β-Glucan was grafted onto the liposomal surface to enable specific targeting of intestinal microfold (M) cells through interaction with the Dectin-1 receptor, thereby facilitating enhanced uptake in Peyer's patches. In spontaneously hypertensive rats, both single-dose and continuous administration of β-glucan-functionalized liposomes resulted in superior antihypertensive effects compared to free peptides and unmodified liposomes. Interestingly, the antihypertensive efficacy was primarily attributed to modulation of the renin-angiotensin system, improved renal and cardiac function, and amelioration of endothelial dysfunction. These findings underscore the potential of the natural polysaccharide β-glucan as a targeting ligand in liposomal systems and highlight the utility of carbohydrate-based materials for enhancing the oral bioavailability and physiological efficacy of bioactive peptides. The proposed strategy offers a promising platform for the development of functional foods or nutraceuticals for hypertension management.