Reversed amphiphilic assembly mechanisms of Pluronic® <scp>F127</scp> in high‐ethanol content

Abstract Pluronic® F127 (Poloxamer 407) is a thermoresponsive triblock copolymer widely used for drug delivery and templating for porous materials, owing to its temperature‐dependent micellization and gelation in aqueous systems. While its self‐assembly behavior in water‐rich or low‐ethanol cosolvents (≤30%) is well established, the molecular behavior of F127 in near‐anhydrous ethanol (90%–100%) remains largely unexplored. Here, we report a reversed self‐assembly mechanism governed by the solubility and crystallinity of the hydrophilic poly(ethylene oxide) (PEO) blocks, rather than the hydrophobic PPO segments that drive micellization in water. F127 remains molecularly dissolved up to ~95% ethanol but undergoes precipitation above this threshold due to collapse of the dehydrated PEO chains. Upon heating, the precipitates reversibly dissolve through melting of PEO crystalline domains, a process confirmed by turbidity and dynamic light scattering analyses. Additionally, tannic acid (TA)—known to strongly hydrogen bond with PEO—modulates the precipitation and re‐dissolution kinetics. These findings highlight a fundamentally distinct assembly mechanism of F127 in ethanol‐rich environments, where solvent polarity and segmental solvation dominate. This study not only provides critical insight into the thermoresponsive behavior of amphiphilic polymers in poor solvents but also expands the potential utility of F127 in ethanol‐dominant drug formulations and soft‐material systems, particularly where aqueous conditions are undesirable.