Associative properties of diblock copolymers used in nanoparticle formation by Flash Nanoprecipitation

Introduction: Flash Nanoprecipitation (FNP) is a nanoparticle (NP) formation technique that relies on amphiphilic diblock copolymer arrested growth of particles achieved through fast solvent/non-solvent mixing. FNP has been... [ view full abstract ]

Introduction: Flash Nanoprecipitation (FNP) is a nanoparticle (NP) formation technique that relies on amphiphilic diblock copolymer arrested growth of particles achieved through fast solvent/non-solvent mixing. FNP has been explored for the NP formation of hydrophobic drugs and imaging agents. A key feature of FNP is providing solvent conditions affording high solute supersaturation and polymer concentrations away from the critical micelle concentration (cmc). These conditions ensure solute nucleation and growth events are concurrent with polymer surface stabilization that arrests particle growth at the sub-micron level, resulting in controlled size NP of organic solutes. Locating the block copolymer cmc is of interest because the kinetics of nucleation and growth involved in the FNP process depend on the level of supersaturation. This study aims at determining the cmc for poly (ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) in tetrahydrofuran/water mixtures, identifying the thermodynamic driving force for micellization, and elucidating the effect of the block length on micellization.
Methods: Dynamic light scattering was used to locate the onset of micellization at various temperatures, and the closed association model to determine the standard thermodynamic functions. Cmc is identified as the point where an increase in light scattering intensity with respect to the signal obtained for dissolved block copolymer is observed. Values for the standard thermodynamic functions were estimated using the cmc values at different temperatures, and the effect of block length evaluated.
Results: The cmc Vs. temperature results show the contribution of the hydrophobic block length on the free energy of micellization, with a free energy contribution of -0.024 KJ/mol per PCL monomer unit. A similar analysis reveals a weaker contribution for the soluble block at constant PCL block length, with a value of -0.0015 KJ/mol per PEG monomer unit.
Discussion: Based on these results, modifying the insoluble block length is an effective approach for tuning cmc. The results map out the micellization domain and reveal the insignificant effect of the soluble block on micellization compared with the insoluble block. These results provide a framework for designing drug formulations via FNP, where high supersaturations of both the drug and the block copolymer are needed.