title: Application of NMR spectroscopy in the development of a biomimetic approach for hydrophobic drug association with physical hydrogels.
abstract: 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.
authors: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, 15782 Santiago de Compostela, Spain.
authors: Rita
authors: R
authors: López-Cebral
authors: Magnetic Resonance Unit, RIAIDT, Campus Vida, University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain.
authors: Manuel
authors: M
authors: Martin-Pastor
authors: Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.
authors: Patrizia
authors: P
authors: Paolicelli
authors: Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy.
authors: Maria Antonietta
authors: MA
authors: Casadei
authors: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, 15782 Santiago de Compostela, Spain; Molecular Image Group, IDIS, Santiago de Compostela University Hospital Complex (CHUS), A Choupana, 15706 Santiago de Compostela, Spain.
authors: Begoña
authors: B
authors: Seijo
authors: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, 15782 Santiago de Compostela, Spain; Molecular Image Group, IDIS, Santiago de Compostela University Hospital Complex (CHUS), A Choupana, 15706 Santiago de Compostela, Spain. Electronic address: alejandro.sanchez@usc.es.
authors: Alejandro
authors: A
authors: Sanchez
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000379:methods*; D002417:Cattle; D000939:Epitopes / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007654:Ketoconazole / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D011239:Prednisolone / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D000939:Epitopes; D020100:Hydrogels; D008024:Ligands; D012710:Serum Albumin, Bovine; D011239:Prednisolone; D007654:Ketoconazole
keywords: Albumin; Binding interaction; Hydrogel; Hydrophobic drug; NMR double titration; NMR-STD