The intestine-responsive lysozyme nanoparticles-in-oxidized starch microgels with mucoadhesive and penetrating properties for improved epithelium absorption of quercetin

Poor solubility and uncontrolled release of hydrophobic compounds greatly inhibit their oral absorption. A lysozyme nanoparticle-in-starch microgel delivery system has been developed to improve the solubility of quercetin (Que) and achieve controlled release by responding to intestinal conditions. Lysozyme (lys) amphiphiles obtained from partial enzymolysis were self-assembled into micelle like lys-nanoparticles (LNP) and Que was encapsulated into their hydrophobic core. Positive charged Que/LNP were then absorbed into oxidized starch microgels (OSM) via electrostatic interaction to establish the pH responsive Que/LNP/OSM composite system. The OSM shell not only protected Que/LNP against the acidic gastric conditions but also exhibited excellent mucoadhesive properties that provided prolonged retention and sustained release of Que/LNP in response to intestinal pH. Subsequently, Que/LNP could penetrate through the mucus layer quickly and be efficiently absorbed by the intestinal epithelium villi. Overall, the LNP/OSM composite system achieved a mucoadhesive-to-penetrating transition in response to intestinal environments, facilitating sustained release and improved epithelium absorption of Que. LNP/OSM showed great potential as smart oral delivery system for hydrophobic compounds to overcome the mucus barriers and improve their absorption.