The effect of pharmaceuticals on the nanoscale structure of PEO–PPO–PEO micelles

We present results on the effects of various hydrophobic drugs and additives on the micellar structure of Pluronic F127 solutions. Small-angle neutron scattering experiments on 5 wt% F127 solutions were used to measure micelle core size (R1), micelle corona size (R2), intermicellar interaction distance (Rint), polydispersity (σ), and aggregation number (Nagg); dynamic light scattering was used to measure critical micelle concentration (CMC); and ultraviolet spectroscopy was used to measure drug solubility and apparent micelle–water partition coefficient (Kmw). The core and corona size were found to generally increase in the presence of the drugs, as did Rint. Both σ and Nagg were found to decrease in the presence of most of the drugs, and the CMC was found to vary considerably with no clear correlation. A design of experiments (DOE) approach was used to analyze the results and build empirical correlations. All of the parameters from the SANS experiments were found to depend strongly on drug solubility, with a weak dependence on Kmw in most cases. The aggregation number, however, was found to depend strongly on both Kmw and solubility. The correlations can be used to roughly predict the structural parameters of F127 micelles for other hydrophobic drugs.