Electrochemically controlled release of anticancer drug methotrexate using nanostructured polypyrrole modified with cetylpyridinium: Release kinetics investigation

A new simple strategy for direct electrochemical incorporation of chemotherapeutic methotrexate (MTX) into conductive polypyrrole (PPy) has been suggested for an electrochemically controlled loading and release system. Electropolymerization of MTX doped polypyrrole yielded poor quality with low efficiency of doping, but a well-doped, nanostructure and increased capacity of drug loading (24.5 mg g(-1)) has been obtained in the presence of cetylpyridinium (CP) as a modifier. When CP was preloaded onto PPy, the hydrophobic surface of the PPy serves as a backbone to which the hydrophobic chain of the CP can be attached. Electrostatic interaction between cationic CP with anionic MIX and aromatic interaction between pyridinium head of CP with pyrimidine and pyrazine rings of MIX increases drug doping. Then release kinetics were investigated at various applied potentials and temperatures. Kinetics analysis based on Avrami's equation showed that the drug release was controlled and accelerated by increasing temperature and negative potential and sustained by increasing positive potential. At open circuit condition, the release parameter (n) represented a diffusive mechanism and at applying electrochemical potentials, a first-order mode. Activation energy parameters (E-a, Delta G(not equal), Delta H-not equal and Delta S-not equal ) and half-life time (t(1/2)) of drug release are also analyzed as a function of applied potential. The nanostructured polymer films (PPy/CP/MTX) were characterized by several techniques: scanning electron microscopy, Furrier transforms Infrared, UV-vis spectroscopy. Overall, our results demonstrate that the PPy/CP/MTX films, combined with electrical stimulation, permit a programmable release of MIX by altering the interaction strength between the PPy/CP and MIX. (C) 2014 Elsevier Ltd. All rights reserved.