Self-assembly of Pluronics L121 in water and added drugs with different hydrophobicity

Pluronic block copolymers are currently employed in a wealth of research applications. In biomedical research, their micelles are well recognized as efficient drug carriers, especially in the treatment of tumors. Here, we study the spontaneous self-assembly and phase behavior of Pluronic L121 in water solutions by hybrid particle-field molecular dynamics simulation. Our approach — together with an appropriate coarse-grain representation of various species composing the solutions — allows us to cover simulation times of the order of microseconds, even for the largest samples, formed by more than 150000 interaction sites (beads). Our study encompasses the whole range of Pluronic concentrations in weight, ϕ=[5−90]% and temperatures between 5 and 60 °C. In agreement with experiments, L121 in water assembles into a lamellar phase, occupying a wide portion of the phase diagram, and bordered by a micellar phase at low concentration and a disordered, highly concentrated phase, at the opposite end. To elucidate the role played by the massive hydrophobic central block, we carry out a comparison with the phase behavior of other lighter Pluronics (L62 and L64), studied within the same modelization and molecular dynamics approach adopted here. Then, we investigate how the addition of two small drug molecules with different affinity with water (namely the hydrophobic ibuprofen, and the hydrophilic gallic acid) influences the overall aggregation properties in the low ϕ regime. We show that the inclusion of ibuprofen significantly speed up the coalescence process into a single aggregate, while the opposite is true with gallic acid. We interpret our evidence in terms of simple hindrance effect on the overall mobility of L121 aggregates.