Protective mechanisms and effects of nano-delivered flavonoids in model cell membranes and neurons
Principal investigator
Flavonoids, polyphenolic biomolecules with antioxidative activity, have recently emerged as potential novel therapeutics for neurodegenerative diseases. In addition to the fact that the mechanisms of their antioxidant effects have not yet been fully elucidated, their applicability is rendered by poor water solubility and chemical instability under physiological conditions encountered during pharmaceutical product consumption. Flavonoid incorporation in nanoparticles (NPs) as carriers has been proposed as possible solution to surpass these obstacles. Therefore, the aim of the proposed project is to overcome the problem of poor water solubility and chemical instability of flavonoids by delivering them loaded in NPs to model membranes and neurons whereby their protective effects should be enhanced. In order to confirm usefulness of this approach, interactions between NPs and cells, in particular, membrane-NP interactions, will be determined since they are of crucial importance both for cell uptake and nanotoxicity.Two kinds of biodegradable mesoporous NPs, silica and goethite, will be investigated as flavonoid nanocarriers. Fe3O4 NPs were chosen as control due to their superior drug-loading and controlled release properties. By applying combination of complementary experimental techniques not yet fully exploited in the field of nanobiotechnology (atomic force microscopy, force spectroscopy, infrared spectroscopy with attenuated total reflection, dynamic light scattering, microcalorimetry), this project will ultimately generate detailed knowledge about the effects of the size, shape, charge and hydrophobicity of NPs loaded with flavonoids on model membranes and neurons, especially under oxidative stress conditions. In addition, information about the changes in structural and nanomechanical properties of model and neuronal membranes will pave the way towards development of novel and improved therapeutic solutions for oxidative stress-associated neurological disorders.