Application of NMR spectroscopy in the development of a biomimetic approach for hydrophobic drug association with physical hydrogels

•Hydrophobic drugs are very interesting therapeutic compounds.•Their incorporation into accurate drug delivery systems is a technological challenge.•A biomimetic approximation was herein developed for this purpose.•A novel NMR strategy permitted the characterization of this approximation.•This NMR strategy has also great potential for other applications.

The clinical application of sparingly soluble drugs is hampered by the wide range of problems associated to their delivery. Herein we present a new physical hydrogel as a delivery system for these drugs. The strategy behind the design of this delivery system involved the incorporation of the protein albumin into the hydrogel with the aim of exploiting its intrinsic capacity to bind small hydrophobic molecules. Prednisolone and ketoconazole were used as model drug molecules. A combination of the saturation transfer difference (STD) spectra and a novel double titration assay followed by NMR was applied to study all of the possible binding modes between albumin and each drug. Finally, the ability of the hydrogel system to release the two model drugs was corroborated. The results of the release studies were in agreement with the drug binding capacities derived from the NMR studies, thus confirming that the potential of the NMR approach as a predictive technique could be useful in evaluating the designs of new drug delivery systems.

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