CHARGE-DEPENDENT AND PH-DEPENDENT BINDING-SITES OF DIPYRIDAMOLE IN IONIC MICELLES - A FLUORESCENCE STUDY

Interaction of the coronary vasodilator dipyridamole (DIP) with micelles of cationic, anionic and zwitterionic detergents has been studied through the use of fluorescence spectroscopy. The aim of this study was to gain insight on the interaction of the drug with the cell membrane. Change of fluorescence emission upon binding allowed to obtain the association constants of both protonated and neutral forms of the drug. The association constants, K-b, were in the range 1.6-3.1 x 10(3) M(-1). The constants for the neutral form of the drug are quite similar for the three micellar systems suggesting a nonspecific binding and a small effect of the charged interface. For the protonated drug, the surface charges modulate the binding, increasing or decreasing it, as a function of electrostatic interactions. The binding constants decrease both for the cationic and zwitterionic micelles implying similar mode of binding while for the anionic micelle the constant increases. Fluorescence quenching using acrylamide and iodide allowed further localization of the drug inside the micelles. In general, binding to micelles decreases significantly the accessibility of the drug as compared to the buffer. For protonated drug, the decrease is similar for the three micelles; in the case of neutral drug for CTAC and HPS the quenching is similar to that of protonated drug suggesting a similar localization in the micelle independently of the charge of the drug, while for SDS the drug is more exposed in the micelle surface. Analysis of the quantum yields and fluorescence lifetimes suggest a significant intramolecular static quenching in the protonated drug.