Host−Guest Chemistry of Dendrimer−Drug Complexes. 3. Competitive Binding of Multiple Drugs by a Single Dendrimer for Combination Therapy

The host−guest chemistry of dendrimer−drug complexes is of great significance to the design and optimization of dendrimer-based drug delivery systems. The competitive binding of multiple drugs by a single dendrimer in aqueous solutions was investigated by 1H NMR and 2D-NOESY studies. These rapid, noninvasive, and accurate NMR techniques allow us to monitor the signals of various drugs as well as carriers in a complicated host−guest system. Ethanol was used as an internal standard to simultaneously quantify dendrimers and drugs and to estimate the binding ability of dendrimers toward different drug molecules. The results suggested that supramolecular structure of dendrimer−multiple drug complexes is formed based on electrostatic interactions and hydrophobic/hydrogen-bond interactions. Factors including hydrophobic properties, sizes, pKa values, charged groups, and spatial hindrance effects of the drugs influenced the localization of drug molecules on the surface and in the interior pockets. In a ternary ho...