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 (1)H 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, pK(a) 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 host-guest system of dendrimer/mycophenolic acid/phenylbutazone, many more phenylbutazone molecules localized in the inner pockets than mycophenolic acid, while more mycophenolic acid bound on the surface by ion-pairs than phenylbutazone. These results provide new insight into host-guest chemistry of dendrimer-drug complexes and the design/optimization of dendrimer-based drug delivery systems.
Laboratory of Functional Membranes, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, PR China.
Libo
L
Zhao
Yiyun
Y
Cheng
Jingjing
J
Hu
Qinglin
Q
Wu
Tongwen
T
Xu
D001667:Binding, Competitive; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004359:Drug Therapy, Combination; D009682:Magnetic Resonance Spectroscopy; D008727:Methotrexate / Q000737:chemistry; D009173:Mycophenolic Acid / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010653:Phenylbutazone / Q000737:chemistry; D012995:Solubility
D050091:Dendrimers; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D010653:Phenylbutazone; D009173:Mycophenolic Acid; D008727:Methotrexate