Structural and functional analysis of polyethylene glycol-coated zein nanoparticles

The development of nanoparticles for drug delivery purposes is faced to a number of challenges, including the complexity of an adequate physico-chemical characterization, especially when nanoparticles are functionalized. The aim of this work was to evaluate and characterize the structure and properties of zein nanoparticles (approximately 200 nm) functionalized with polyethylene glycol (PEG 35,000) at different PEG-to-zein ratios. The interaction between PEG and zein, attributed to hydrogen bonding between the amide groups of zein and the hydroxyl groups of PEG, was evidenced by FTIR and further confirmed by 2D-COS spectroscopy. DSC and TGA thermograms demonstrated the role of PEG in improving nanoparticle thermal stability, with PEG-coated nanoparticles exhibiting higher decomposition temperatures and increased PEG content with higher PEG-to-zein ratios. SEM and AFM imaging of nanoparticle thin films confirmed that PEG decoration enhanced wettability and reduced the hydrophobicity of bare zein nanoparticles, consistent with Rose Bengal test results. Additionally, AFM analysis of nanoparticle distribution in a mucin thin film demonstrated that PEG coating improved nanoparticle dispersibility within the mucin matrix, in line with previous studies describing the increased diffusivity and mucus-permeation properties of nanoparticles coated with hydrophilic polymers. In summary, this study highlights the importance of an in-depth analysis of the physicochemical characteristics of nanoparticles, providing valuable structural insights that facilitate optimization and the selection of the most suitable compositions for preclinical development.