pH-Responsive behavior of bis-MPA-COOH dendrimer as a drug carrier studied at liquid|liquid interfaces

• Specific association of antitumor drugs with bis-MPA-COOH dendrimer. • Spectroelectrochemical analysis of dendrimers as stimuli-responsive drug carriers. • Phase-transfer mechanism of drugs tunable by the association with dendrimers. The polyester dendrimer based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) with neutral interior and peripheral carboxy groups, bis-MPA-COOH dendrimer was examined as a stimuli-responsive drug carrier at the water|1,2-dichloroethane (DCE) interface. The bis-MPA-COOH dendrimer formed ion associates with cationic fluorescent probe and antitumor drugs under physiological pH conditions. The interfacial behavior of bis-MPA-COOH dendrimers and their ion associates with cationic drugs was analyzed in detail by the ion transfer voltammetry and potential-modulated fluorescence (PMF) technique. The bis-MPA-COOH dendrimers exhibited adsorption properties at the water|DCE interface, depending on the dendritic generation and the charged state. The ion association between anthracycline antibiotics, daunorubicin (DNR) and doxorubicin (DOX), and bis-MPA-COOH dendrimers was affected by a minor structural difference of drug molecules, where the monocationic DNR showed a stable association. The mono and diprotonated mitoxantrone (MTX) were also associated stably with the bis-MPA-COOH dendrimer. The guest drug ions were effectively released from their dendrimer associates by applying appropriate potentials and transferred across the water|DCE interface. The pH-dependence of the ion association was quantitatively estimated from the shift of the ion transfer potential of cationic drugs at the water|DCE interface. The results demonstrated that the bis-MPA-COOH dendrimer provides useful functionality for pH-responsive drug carriers.