The effects of Pluronic block copolymers on the aggregation state of nystatin

The purpose of this work was to characterize the effect of block copolymer composition on the aggregation state of nystatin in the presence of Pluxonic micelles. The critical aggregation concentrations (CACs) of nystatin were determined by dynamic light scattering (DLS). The CAC of nystatin in phosphate-buffered saline was 20 muM at 37 degreesC. Addition of Pluronics significantly increased the CAC of nystatin up to >350 muM at 37 degreesC at the concentrations studied. The CAC values corresponded directly to the size of the Pluronic hydrophobic blocks, and inversely with Pluronic critical micellization concentration (CMC). Predictably, increasing Pluronic concentration and temperature revealed increases in CACs. The micelle-water partition coefficient (P) of nystatin was determined by nystatin fluorescence. The P for nystatin at 37 degreesC was calculated in F68, F98, P105, and F127 to be 15, 21, 73, and 79, respectively. Pluronic micelle core polarity experiments, determined by pyrene fluorescence, revealed decreased polarity with increasing hydrophobic block length and temperature. Thus, nystatin CACs in the presence of Pluronics correlated directly with the partition coefficients, and inversely with core polarity. These results point to the number of micelles in solution as the primary factor responsible for nystatin solubilization by Pluronics. (C) 2004 Elsevier B.V. All rights reserved.