# pH-responsive self-assembly of quercetin-loaded zein-sodium caseinate-fucoidan hybrid nanoparticles: nanostructure, stability and in vitro digestive behavior

## TL;DR

Researchers created stable nanoparticles to deliver quercetin, a healthful compound, using a pH-sensitive method that improves its solubility and stability for food and pharmaceutical use.

## Contribution

A novel pH-driven method to create quercetin-loaded hybrid nanoparticles with enhanced stability and controlled release behavior.

## Key findings

- The nanoparticles showed excellent stability under various conditions, including high salt, heat, and storage.
- Quercetin release was minimal in gastric fluid but significantly higher in intestinal fluid, indicating targeted delivery potential.
- The hybrid system demonstrated high quercetin loading efficiency and a spherical morphology stabilized by multiple interactions.

## Abstract

Quercetin (Que), a physiologically versatile flavonoid, faces application limitations in food and pharmaceuticals due to poor aqueous solubility and stability.

To address this, we developed quercetin-loaded zein-sodium caseinate-fucoidan (Que-ZE-SC-FD) ternary nanoparticles using a green, pH-driven approach.

The Que-ZE-SC-FD nanoparticle exhibited a spherical morphology stabilized by hydrogen bonding, electrostatic, and hydrophobic interactions, with a mean diameter of 137.8 ± 11.6 nm, PDI of 0.38 ± 0.04, z-potential of 34.9 ± 0.6mV, and high quercetin loading efficiency (92.8% ± 1.1%). Crucially, SC and FD demonstrated synergistic stabilization effects. The Que-ZE-SC-FD nanoparticle exhibited a mean particle size of 150.8 ± 0.6 nm at a pH of 8.0, and solution remained clear and transparent with no observable sediment. Under a NaCl concentration of 3.0 mol/L, the particle size decreased to 127.8 ± 4.5 nm. Upon heating at 80°C for 2 h, the particle size further reduced to 121.3 ± 1.2 nm, with a PDI of 0.34 ± 0.02. After 28 days of storage, the particle size decreased to 125.1 ± 1.9 nm, while the PDI decreased slightly to 0.32 ± 0.01 and the zeta potential increased to 31.6 ± 1.5mV, collectively indicating excellent stability. Under simulated gastrointestinal conditions, the Que release from ZE-SC-FD nanoparticles was only 22.2 ± 0.5% in gastric fluid; however, a significantly higher release rate of 75.0 ± 0.5% was achieved in intestinal fluid. These results demonstrate that ZE-SC-FD nanoparticles serve as a robust nanocarrier system for encapsulating, protecting, and delivering quercetin.

Infographic illustrating the process and analysis of quercetin-loaded nanoparticles. It shows the deprotonation and unfolding of zein, sodium caseinate, and fucoidan for nanoparticle formation at different pH levels. Charts depict fabrication details and stability, with microscopic images showing nanoparticle structure. Test tubes display visual stability results under various conditions. A graph of in vitro simulated gastrointestinal digestion is included, along with an illustration of the digestive system.