Croy Scott R, Kwon Glen S
Department of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705-2222, USA.
J Control Release. 2004 Mar 5;95(2):161-71. doi: 10.1016/j.jconrel.2003.11.003.
The purpose of this work was to characterize the effect of block copolymer composition on the aggregation state of nystatin in the presence of Pluronic 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 microM at 37 degrees C. Addition of Pluronics significantly increased the CAC of nystatin up to >350 microM at 37 degrees C 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 degrees C 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.
这项工作的目的是表征在普朗尼克胶束存在下，嵌段共聚物组成对制霉菌素聚集状态的影响。通过动态光散射（DLS）测定制霉菌素的临界聚集浓度（CAC）。在37℃时，制霉菌素在磷酸盐缓冲盐水中的CAC为20μM。在所研究的浓度下，添加普朗尼克显著提高了制霉菌素的CAC，在37℃时高达>350μM。CAC值与普朗尼克疏水嵌段的大小直接相关，与普朗尼克临界胶束浓度（CMC）呈反比。可以预见，增加普朗尼克浓度和温度会导致CAC增加。通过制霉菌素荧光测定制霉菌素的胶束-水分配系数（P）。在F68、F98、P105和F127中，37℃时制霉菌素的P分别计算为15、21、73和79。通过芘荧光测定的普朗尼克胶束核心极性实验表明，随着疏水嵌段长度和温度的增加，极性降低。因此，在普朗尼克存在下制霉菌素的CAC与分配系数直接相关，与核心极性呈反比。这些结果表明溶液中胶束的数量是普朗尼克增溶制霉菌素的主要因素。
