AbstractChemically modified starch nanoparticles (NPs) have attracted significant scientific attention due to their versatility and broad applications. Despite substantial research on starch NPs formulation, approaches to starch modification for both conventional and novel uses remain underexplored. Native starch suffers from low shear stress, hydrophilicity, poor thermal properties, and limited resistance to digestion and retrogradation, necessitating modifications via physical, chemical, enzymatic, or genetic methods. Ultrasound‐assisted physical and chemical modification presents an efficient solution. This study synthesizes starch propionate NPs (SPNPs) through a single emulsification solvent evaporation method employing ultrasonication. The synthesis parameters are adjusted for particle size using a three‐factor, three‐level Box–Behnken design. The research examines the effects of polymer concentration, sonication energy, and sonication time, revealing that sonication time significantly impacts SPNPs size more than the other variables. Under optimized conditions, the predicted SPNPs size is 97.5 nm, with an actual observed size of 105 nm, indicating a strong correlation and validating the model’s reliability. The findings underscore the model’s effectiveness in producing size‐consistent nanoformulations, bolstering their potential as effective drug delivery vehicles.
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