Development and Optimization of Zein Nanoparticles for Gastric Delivery and Controlled Release of Styrax Liquidus

Gastric ulcer, a common gastrointestinal inflammatory disorder, and gastric cancer, a leading digestive malignancy, remain serious global health concerns. Styrax liquidus (SL) possesses strong antioxidant, anti-inflammatory, antiseptic, and gastroprotective properties. This study reports the development of zein nanoparticles containing SL (ZNPs) for targeted gastric delivery. Nanoparticles were prepared using nanoprecipitation (NP) and flash nanoprecipitation (FNP) techniques and characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), ultraviolet–visible spectroscopy, and in-vitro digestion analysis. Process optimization was carried out through response surface methodology (RSM) with a D-optimal custom design to evaluate the influence of zein concentration, SL ratio, flow rate, and mixing speed on particle size, polydispersity index, zeta potential, encapsulation efficiency, and release behavior. The optimized ZNPs showed smooth, spherical morphology with particle sizes ranging from 183.18 to 225.59 nm and encapsulation efficiencies of 71.24% (NP) and 82.64% (FNP). Gastric release of SL varied between 58.17% and 88.58%. Among the formulation variables, zein concentration and SL ratio were identified as the most significant factors, while FNP produced more stable and homogeneous particles. Both nanoparticle types exhibited notable anti-ulcer activity, with IC50 values of 195.2 µg/mL for NP and 189.3 µg/mL for FNP. In addition, the optimized ZNPs displayed stronger antiproliferative effects against AGS gastric cancer cells than free SL at lower concentrations. These findings demonstrate that zein-based nanocarriers of Styrax liquidus represent a promising platform for targeted gastric therapy by integrating controlled release with enhanced therapeutic efficacy.