Localization of dipyridamole molecules in ionic micelles: effect of micelle and drug charges

The localization of the coronary vasodilator dipyridamole (DIP) in cationic cetyltrimethylammonium chloride (CTAC), anionic sodium dodecylsulfate (SDS) and zwitterionic N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate and lysophosphatidylcholine (HPS and LPC) micelles was investigated using fluorescence quenching by quenchers with known localization in the micelle (TEMPO and 5-doxyl and 12-doxyl stearic acids). The use of fluorescence quenching jointly with fluorescence and 1H-NMR spectral measurements shows that DIP molecules in both protonated and nonprotonated forms are localized in micelles near the region which separates their polar and nonpolar parts, the polarizable heteroaromatic cycle of DIP being close to the polar part and the nonpolar substituents penetrating the hydrophobic interior of the micelle. The electrostatic interaction between the protonated DIP molecules and micelle charges either moves DIP into the micelle interior (for cationic and zwitterionic micelles) or draws it closer to the micelle surface (for anionic ones). Our results could be relevant to the mechanism of DIP action since many data indicate the interaction of the drug with cell membranes. The ability of DIP to localize near the membrane surface with the substituents immersed into a hydrophobic moiety could be essential for the drug interaction with P-glycoprotein, which is responsible for mediation of the effects of several antitumour drugs.