Effect of PPO/PEO Ratio on the Phase Behavior of Reverse Pluronics

The specific features of the phase diagrams of aqueous Pluronic systems, and particularly those of reverse Pluronics, are critically important for their broad range of applications, notably as nanocarriers for anticancer molecules. This work aims to investigate the effect of increasing hydrophobicity, achieved by varying the PPO/PEO ratio and the molecular weight, on the phase behavior of three reverse Pluronics: 10R5 [(PPO)₈-(PEO)₂₂-(PPO)₈], 17R4 [(PPO)₁₄-(PEO)₂₄-(PPO)₁₄] and 31R1 [(PPO)₂₆-(PEO)₇-(PPO)₂₆]. A broad set of physical measurements, including density, sound velocity, viscosity, and surface tension, was used to characterize the physical properties of the solutions. These data were complemented by additional techniques such as direct observation, dynamic light scattering, and rheological measurements. Based on the primary measurements, molar volume, apparent adiabatic compressibility, and hydration profiles were subsequently derived. Phase diagrams were constructed for each system over concentration ranges of 0.1-90 wt.% and temperatures between 6 and 70 °C, identifying distinct regions corresponding to random networks, flower-like micelles, and micellar networks. Notably, the 31R1/water system does not form flower-like micelles, whereas both the 17R4/water and 10R5/water systems display such structures, albeit in a narrow interval, that shift toward higher concentrations and temperatures with increasing PPO/PEO ratio. Altogether, the present study provides new insights into the physicochemical behavior of reverse Pluronic systems, offering a foundation for their rational design as hydrophobic nanocarriers, either as standalone entities or in conjunction with other copolymers.