Impact of pluronic F127 on aqueous solubility and membrane permeability of antirheumatic compounds of different structure and polarity

摘要

Solubilization of the disease modifying antirheumatic drugs (methotrexate, leflunomide and sulfasalazine) in micelles of amphiphilic triblock copolymer Pluronic F127 was studied in buffers with physiological pH. The solubilization follows the order leflunomide sulfasalazine methotrexate. It was found that the size and ionization state of the drug molecules play an important role in the binding with the Pruronic F127 micelles. The higher solubilizing effect of Pluronic F127 on leflunomide can be caused by smaller geometrical dimensions and higher hydrophobicity of this drug. The 10 H-1 and 2D ROESY NMR, UV-vis spectroscopy and dynamic light scattering experiments were used to get insight into the interaction between Pluronic F127 micelles and antirheumatic drugs in aqueous solutions. Among the drugs under consideration only leflunomide can be located in the micelle core more deeply. Effect of Pluronic F127 on membrane permeability was also examined using Permeapad (TM) barrier imitating the membranes of the intestinal epithelium. It was found that solubilizing effect of Pluronic F127 is accompanied by decrease of drug permeability. (C) 2018 Published by Elsevier B.V.