Synergistic Effect of Binary Mixed-Pluronic Systems on Temperature Dependent Self-assembly Process and Drug Solubility

Mixed Pluronic micelles from very hydrophobic and very hydrophilic copolymers were selected to scrutinize the synergistic effect on the self-assembly process as well as the solubilization capacity of ibuprofen. The tendency of mixing behavior between parent copolymers was systematically examined from two perspectives: different block chain lengths at same hydrophilicity (L92 + F108, + F98, + F88, and + F68), as well as various hydrophobicities at the same PPO moiety (L92 + F88, + F87, and + P84). Temperature-dependent micellization in these binary systems was clearly inspected by the combined use of high sensitivity differential scanning calorimeter (HSDSC) and dynamic light scattering (DLS). Changes in heat capacity and size of aggregates at different temperatures during the whole micellization process were simultaneously observed and examined. While distinction of block chain length between parent copolymers increases, the monodispersity of the binary Pluronic systems decreases. However, parent copolymers with distinct PPO moieties do not affirmatively lead to non-cooperative binding, such as the L92 + P84 system. The addition of ibuprofen promotes micellization as well as stabilizes aggregates in the solution. The partial replacement of the hydrophilic Pluronic by a more hydrophobic Pluronic L92 would increase the total hydrophobicity of mixed Pluronics used in the system to substantially enhance the solubility of ibuprofen. The solubility of ibuprofen in the 0.5 wt % L92 + 0.368 wt % P84 system is as high as 4.29 mg/mL, which is 1.4 times more than that of the 0.868 wt % P84 system and 147 times more than that in pure water at 37 degrees C.