Polysorbate 80 and Cremophor EL Micelles Deaggregate and Solubilize Nystatin at the Core-Corona Interface

The extent and the location of nystatin solubilization by nonionic surfactant micelles were determined. The critical aggregation concentrations (CAC) of nystatin in 4 × 10−3 M surfactant were determined by dynamic light scattering. The resulting CAC values for nystatin in Cremophor EL (CrEL), Tween 80 (T80), and Nofable ESO-9920 (NOF) were 150, 150, and 300 µM compared to 10 µM for the phosphate-buffered saline (PBS) control. The surfactants were able to solubilize and deaggregate nystatin from 50 to 75 times more than the PBS control. The core polarity of CrEL micelles, determined by pyrene fluorescence, was significantly lower than T80 and NOF micelles. The micelle-water partition coefficients (P) of nystatin and pyrene were determined by fluorescence spectroscopy. The partition coefficient values of 7.5 µM nystatin in CrEL and NOF micelles were 1100 ± 60 and 1000 ± 110, an insignificant difference (p > 0.1). However, there was a significant increase in pyrene partitioning in micelles with lower core polarity. Additionally, the P of nystatin decreased when the nystatin concentration was increased, whereas the pyrene P did not. The unusual partitioning behavior of nystatin revealed a good fit with the Langmuir adsorption isotherm, indicating solubilization at the micellar core-corona interface.