Gliadin-fucoidan nanoparticles enable pH-responsive drug delivery and attenuate Sepsis-associated acute kidney injury.

Abstract

Gliadin and fucoidan are biologically active macromolecules with complementary self-assembly, drug-binding, and anti-inflammatory properties. Here, gliadin/naringenin@fucoidan nanoparticles (NPs) were engineered through antisolvent precipitation followed by electrostatic self-assembly to improve the oral delivery and renoprotective activity of naringenin. Gliadin, a 35-40 kDa wheat protein, formed the hydrophobic drug-loaded core, whereas sulfated fucoidan formed a functional polysaccharide shell through electrostatic interactions and hydrogen bonding. The NPs exhibited spherical core-shell morphology, a transmission electron microscopy diameter of 100-110 nm, a hydrodynamic diameter of 108.3 nm, and a pH-dependent surface charge. Nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and X-ray diffraction confirmed gliadin-naringenin molecular interactions, fucoidan surface deposition, and conversion of crystalline naringenin into an amorphous molecular dispersion. The optimized formulation achieved 41.11% encapsulation efficiency and a loading capacity of 30.83 μg/mL. Fucoidan coating restricted naringenin release to 13.95% at pH 2.0 but increased release to 77.15% at pH 7.0. In lipopolysaccharide (LPS)-injured HEK-293 cells, the core-shell NPs restored viability to 93.18%, reduced reactive oxygen species from 181.0 to 74.3, and limited early and late apoptosis to 4.35% and 4.58%, respectively. Cellular fluorescence intensity increased 7.7-fold relative to free naringenin. In septic acute kidney injury mice, oral treatment reduced blood urea nitrogen, creatinine, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin to 7.10 mmol/L, 25.05 μmol/L, 94.87 pg/mL, and 177.37 ng/mL, respectively. These findings establish gliadin-fucoidan macromolecular assembly as a pH-responsive and biologically functional oral nanoplatform for renal inflammation.