Doctor of Philosophy (PhD)
Engineering Science (Interdepartmental Program)
The goal of the study was to develop antioxidant polymeric nanoparticles as a new delivery system for food and pharmaceutical applications. Natural antioxidants like alpha-tocopherol, vitamin C, and carnosine, are responsible to protect biological systems against free radicals attack. The conjugation of vitamin C-vitamin E (EC) and alpha-tocopherol-carnosine (VECAR) were performed to obtain antioxidant surfactants which were used for polymeric nanoparticle synthesis. The surfactant made of á-tocopherol (vitamin E) and ascorbic acid (vitamin C) of antioxidant properties dubbed as EC was used to make poly(lactic-co-glycolic) acid (PLGA) nanoparticles. Self-assembled EC nanostructures and PLGA-EC nanoparticles were made by nanoprecipitation, and the nanoparticle physical properties were studied at different salt concentrations, surfactant concentrations, and polymer:surfactant ratios. EC was soluble in polar solvents, and Span 80 was selected as a control due to its similar surfactant properties. The PLGA-EC nanoparticles and EC surfactant showed antioxidant activity based on DPPH technique and EPR study, which is not characteristics to commercially available Span80. The newly synthesized EC surfactant was found successful in forming uniform, small size polymeric nanoparticles of intrinsic antioxidant properties. The next step was to synthesize VECAR, an antioxidant molecule made of carnosine and alpha-tocopherol derivative. The designed molecule looks for protection of low density lipoproteins (LDL) from oxidation by placing at the LDL interface two potent natural antioxidants. The LDL protection can impact the development and outcome of atherosclerosis. The approach followed was to use the phytyl chain as active site for coupling of carnosine. The synthesis process involved 8 steps starting with esterification of Trolox and finishing with the deprotection of the hydroxyl group of the alpha-tocopherol moiety. The antioxidant behavior of VECAR (0.0236 mM) was tested by DPPH assay which showed values similar to pure alpha-tocopherol (0.0229 mM). The values suggested full recovery of the active hydroxyl group of the alpha-tocopherol derivative. More studies are needed to test antioxidant behavior in the presence of lipids and ability of VECAR to protect LDL oxidation in vitro; in vivo analysis of LDL oxidation in the presence of VECAR is required to understand the fate of VECAR in more complex and real systems.
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Astete R., Carlos Ernesto, "Antioxidant Nanoparticles as Delivery Systems" (2010). LSU Doctoral Dissertations. 195.