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Investigation of lipid peroxidation in model membranes and enhanced protection using flavonoid embedded nanoparticles

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 activity have not yet been fully elucidated, their applicability is limited 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 a possible solution to surpass these obstacles. Mesoporous NPs were selected with the goal to increase the flavonoid loading and entrapment efficiency, and to enable protection of flavonoids in physiological conditions. This research will ultimately generate detailed knowledge about the effects of the size, shape, charge, and hydrophobicity of NPs with embedded flavonoids and their controlled release. The model membranes made of an unsaturated lipid (DOPC) with and without embedded flavonoids were investigated with the respect to flavonoid influence on the membrane structure, elasticity, and its functionality, especially regarding lipid order. Model lipid membranes were studied before and after lipid peroxidation (LP), which was induced by addition of H2O2 and Fe2+. By combining AFM imaging, force spectroscopy (FS), and ATR FTIR spectroscopy, the new approach was established to gain insight into flavonoid protective mechanism towards the oxidative stress, as well as the altered nanomechanics and structural reorganization of the membrane after inducing peroxidation. Also, liposome zeta potential and hydrodynamic diameter measurements were performed before and after LP to gain more insight into stability and charge of the liposome suspension during the reaction. The research aim is to overcome the problem of poor water solubility and chemical instability of flavonoids by delivering them loaded in biodegradable mesoporous NPs to model membranes, as well as to study flavonoid interactions with model lipid membranes in vitro before and after induced lipid peroxidation.

flavonoids ; lipid peroxidation ; nanoparticles ; antioxidants

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