Effect of PEG molecular weight on the physicochemical properties of zein nanoparticles: A comparative study

Polyethylene glycol (PEG) surface modification of protein-based nanoparticles is widely used to enhance colloidal stability, with potential applications in drug delivery. Despite its widespread use, the influence of PEG molecular weight on the behavior of PEG decorated zein nanoparticles remains insufficiently understood. Here, we investigate how PEG MW and PEG-to-zein ratio governs the structural and physicochemical properties of zein nanoparticles. Nanoparticles functionalized with PEG of 8, 20, and 35 kDa were characterized using a multiscale approach combining nanoscale analysis (particle size, zeta potential, FT-IR 2D-COS, titration, and thermogravimetric analysis) with thin-film surface characterization (water contact angle, roughness and atomic force microscopy). All formulations exhibited sizes of approximately 200 nm, low polydispersity, and similar surface charge (-45 mV), indicating preserved colloidal integrity across systems. However, PEG molecular weight and PEG-to-zein ratio were associated with differences in interfacial organization of PEG decorated zein nanoparticles. In addition, PEG 8 kDa enhanced surface hydrophilicity and hydroxyl exposure, suggesting a higher surface PEG density, whereas PEG 35 kDa was associated with more ordered interfacial features with enhanced colloidal and thermal stability. Notably, PEG 20 kDa provided the best compromise between surface coverage and stability. Overall, PEG molecular weight and PEG-to-zein ratio emerge as key designs for tuning the properties of zein nanoparticles, enabling precise control over structure, stability, and surface functionality through a simple molecular design strategy.