Utilizing Melting Point as a Nanoscale Probe to Evaluate Domain Sizes in the Polyethylene Glycol–Water System

Polyethylene glycol (PEG)-based polymers are widely used as matrices in drug delivery systems (DDSs) due to their excellent biocompatibility and hydrophilicity. In such systems, drug molecules are typically encapsulated within PEG–water domains ranging from tens to 100 nm in size. The size of domains plays a critical role in the design and performance of DDS materials. In this study, we investigated the nanoscale dependence of the PEG–water phase transition temperature at sub-room temperatures using differential scanning calorimetry. Our results reveal that the melting point of PEG–water domains decreases with decreasing domain size regardless of the polymer concentration. This size-dependent melting behavior is well-described by a simplified Gibbs–Thomson equation. Based on this relationship, we propose a straightforward method for estimating the size of unknown PEG–water domains through melting point in controlled silica pore material measurements, providing a practical approach for evaluating DDS formulations. Additionally, our findings indicate that PEG–water solutions confined within mesopores consistently exhibit a eutectic composition regardless of concentration, highlighting potential applications in nanopore-based separation technologies.