Synthesis and Antioxidant Activity of Nitroxide Functionalized Lipids

Liposomes are biodegradable and nonimmunogenic vesicular structures made of amphipatic phospholipids which can encapsulate both hydrophilic and hydrophobic materials; because of their versatility they are used as carriers in drugs and gene delivery systems. Polyunsaturated fatty acids present in the bilayer are susceptible to oxidative damage which can alter some important properties like fluidity and permeability and can cause system delivery destruction. The mechanism of lipids oxidative degradation may involve free radical reactions that lead to changes in the unsaturated systems present and eventually to the degradation of the lipid chains. In order to maintain their physical, chemical and functional properties, liposomes need to be protected by antioxidant compounds that can delay or prevent oxidation upon reaction with radical species. Nitroxide radicals (paramagnetic compounds with the unpaired electron mainly localized on the N-O group) are known to protect biological system against oxidative processes in different media and under different stress conditions. [1] As part of our ongoing research in the field of nitrones [2] and nitroxides [3] as potential antioxidants we synthesized neutral non zwitterionic lipids labeled by nitroxide able to react with radical species. Multilamellar liposomes were prepared by mixing the new lipids with Phosphatidylcholine and their EPR features and antioxidant activity was studied.