Amphiphilic Cyclodextrin Nanoparticles as Delivery System for Idebenone: A Preformulation Study
Federica De Gaetano,
Angela Scala,
Consuelo Celesti,
Kim Lambertsen Larsen,
Fabio Genovese,
Corrado Bongiorno,
Loredana Leggio,
Nunzio Iraci,
Nunzio Iraci,
Antonino Mazzaglia,
Cinzia Anna Ventura
Affiliations
Federica De Gaetano
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy
Angela Scala
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy
Consuelo Celesti
Department of Engineering, University of Messina, Contrada Di Dio, 98166 Messina, Italy
Kim Lambertsen Larsen
Department of Chemistry and Bioscience, Aalborg University, Frederik Bajers Vej 7H, 9220 Aalborg, Denmark
Fabio Genovese
Technical, Economic and Technological Institute “Girolamo Caruso”, Via John Fitzgerald Kennedy 2, 91011 Alcamo, Italy
Corrado Bongiorno
National Council of Research, Institute of Microelectronics and Microsystems (CNR-IMM), Strada VIII n. 5-Zona Industriale, 95121 Catania, Italy
Loredana Leggio
Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Torre Biologica, Via Santa Sofia 97, 95125 Catania, Italy
Nunzio Iraci
Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Torre Biologica, Via Santa Sofia 97, 95125 Catania, Italy
Nunzio Iraci
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy
Antonino Mazzaglia
National Council of Research, Institute for the Study of Nanostructured Materials (CNR-ISMN), URT of Messina c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences of the University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, Italy
Cinzia Anna Ventura
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy
Idebenone (IDE), a synthetic short-chain analogue of coenzyme Q10, is a potent antioxidant able to prevent lipid peroxidation and stimulate nerve growth factor. Due to these properties, IDE could potentially be active towards cerebral disorders, but its poor water solubility limits its clinical application. Octanoyl-β-cyclodextrin is an amphiphilic cyclodextrin (ACyD8) bearing, on average, ten octanoyl substituents able to self-assemble in aqueous solutions, forming various typologies of supramolecular nanoassemblies. Here, we developed nanoparticles based on ACyD8 (ACyD8-NPs) for the potential intranasal administration of IDE to treat neurological disorders, such as Alzheimer’s Disease. Nanoparticles were prepared using the nanoprecipitation method and were characterized for their size, zeta potential and morphology. STEM images showed spherical particles, with smooth surfaces and sizes of about 100 nm, suitable for the proposed therapeutical aim. The ACyD8-NPs effectively loaded IDE, showing a high encapsulation efficiency and drug loading percentage. To evaluate the host/guest interaction, UV-vis titration, mono- and two-dimensional NMR analyses, and molecular modeling studies were performed. IDE showed a high affinity for the ACyD8 cavity, forming a 1:1 inclusion complex with a high association constant. A biphasic and sustained release of IDE was observed from the ACyD8-NPs, and, after a burst effect of about 40%, the release was prolonged over 10 days. In vitro studies confirmed the lack of toxicity of the IDE/ACyD8-NPs on neuronal SH-SY5Y cells, and they demonstrated their antioxidant effect upon H2O2 exposure, as a general source of ROS.
