In situ SAXS and rheological correlation of microstructural evolution during the sol-gel transition of Poloxamer 407...

The sol-gel transition temperature (T_sol-gel) of poloxamer 407 (P407) strongly depends on concentration, limiting its application in thermoresponsive pharmaceutical systems that require gelation between ambient and physiological temperatures. Incorporation of the more hydrophilic poloxamer 188 (P188) is known to modify T_sol-gel in a non-monotonic manner, but the mechanism governing this behavior and its relationship to thermally induced structural and rheological evolution remain unresolved. In this study, 20 wt% P407 solutions containing 5-20 wt% P188 were examined using differential scanning calorimetry (DSC), temperature-sweep rheology, and in situ synchrotron small-angle X-ray scattering (SAXS) under identical heating conditions (1 °C/min) to elucidate temperature-dependent micellization, viscoelasticity, and structural organization. DSC results showed that increasing P188 lowered both the critical micellization temperature and enthalpy, suggesting the formation of smaller, less cooperative micelles and preferential localization of P188 at micelle coronas rather than co-micellizing with P407. Rheological measurements revealed a trend reversal in T_sol-gel, increasing to 31.7 °C at 10 wt% P188 with reduced elasticity and decreasing to 24.5 °C at 20 wt% P188, where stronger gels formed. SAXS analysis demonstrated that gelation in all mixtures began with a disordered micellar network that evolved into ordered phases upon heating, with FCC lattices prevailing at lower P188 contents and coexisting FCC/BCC phases with reduced intermicellar spacing emerging at higher P188 levels. These findings suggest that P188 modulates gelation through competing effects: an upward T_sol-gel trend at low concentrations due to hydrated P188 chains disrupting micelle packing, and a downward trend at higher concentrations driven by densification and corona entanglement of numerous smaller micelles. This work establishes a mechanistic basis for the non-monotonic shift in T_sol-gel observed in mixed P407/P188 systems and deepens understanding of structural-rheological coupling in thermoresponsive block-copolymer hydrogels.