Structure determination of cyclodextrin derivatives and cyclodextrin complexes by NMR spectroscopy: comparative analysis of the molecular architectures
As more than half of new candidates exhibit low solubility and selectivity in target organisms, the increase of solubility and bioavailability e.g. via excipients (cyclodextrin etc.) are crucial for the formulation and utilization. Cyclodextrins (CD) are a family of biocompatible oligosaccharides with a cavity, in which many active compounds can be hosted. Many CD-based derivatives are widely used as delivery systems due to their low toxicity and absence of immune stimulation even at high dosage.
Our approach is based on the synthesis and characterisation mono- and multivalent cyclodextrin derivatives and their drug complexes. We will determine and compare the structure and stability of the mono- and multivalent constructs and the drug complexes. Our “pilot study” will provide structure – activity relations in order to design optimized cyclodextrin host molecules (polarity, ring size etc.). Further we will investigate hydroxypropyl-β-cyclodextrins and their NODAGA complexes to evaluate in vivo biodistribution studies.
The combined use of 1D- and 2D versions of high-resolution 1H- and 13C-NMR spectroscopy is indispensable for the successful accomplishment of the project. Among them, the highly time-consuming correlation methods, suitable to mapping the network of chemical bonds between the incorporated molecular fragments, are of pronounced importance. The formation of molecular complexes can be detected through the changes in the chemical shifts and by the assessment of the appropriate interatomic distances.
We would like to prove that cyclodextrin based carrier are promising candidates as target cell specific delivery vehicles and as carriers for in vivo imaging to determine biodistribution of drug candidates with different chemical features.
Szilvia Bősze, Kata Horváti, Antal Csámpai