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.