Ion transfer and adsorption behavior of ionizable drugs affected by PAMAM dendrimers at the water|1,2- dichloroethane interface

Abstract

The transfer and adsorption reactions of ionizable drug molecules, i.e. dipyridamole (DIP), propranolol (PRO) and warfarin (WAR), at the water|1,2-dichloroehtane (DCE) interface were studied in the presence of the carboxylate- terminated generation 3.5 (G3.5) or amino-terminated generation 4 (G4) polyamidoamine (PAMAM) dendrimers. The ionic partition diagram of the ionizable drugs was determined through the voltammetric analysis of ion transfer responses. In the DIP system, the additional voltammetric responses associated with the interfacial adsorption were observed in the positive potential region. Although the spectroscopic features of the drug species in the aqueous solution were hardly affected by the addition of the dendrimers, the ion transfer currents in the DIP and PRO systems were decreased in the presence of the G3.5 PAMAM dendrimer indicating the intermolecular association between the cationic drugs and negatively charged dendrimers in the interfacial region. The interfacial mechanism of the fluorescent DIP species was investigated in detail by potential-modulated fluorescence (PMF) spectroscopy. The PMF results demonstrated that the monoprotonated form, HDIP+, was transferred across the water|DCE interface accompanied by the adsorption process. The interfacial mechanism of the DIP species was significantly modified by the dendrimer, depending on the pH condition. Under acidic conditions, the positively charged G3.5 PAMAM dendrimer adsorbed at the interface effectively prevented the coadsorption of HDIP+. At higher pHs, DIP (or HDIP+) interacted with the hydrophobic interior moiety (or negatively charged periphery) of the dendrimers.