Antioxidant Activity of \316\261- and \316\264- Tocopheryl Ester and Carbonate Co- drugs on UV-induced Lipid Peroxidation in Skin
Loading...
Issue Date
2014
Authors
Sodvadia, Ritesh '14
Degree
MS in Pharmaceutical Sciences
Advisor
Hass, Martha A.
Committee Members
Voigt, Jeffrey M.
Feleder, Carlos
Feleder, Carlos
Journal Title
Journal ISSN
Volume Title
Abstract
Exposure to ultraviolet radiation (UVR) is one of the major factors causing deterioration of the skin. Reactive oxygen species (ROS) generated in skin due to exposure to UVR contributes to the development and progression of damage and disease in the skin. Topical antioxidant (AO) co-drugs, tocopherylester (TOCE) and tocopherylcarbonate (TOCC), synthesized from tocopherol (TOC) and lipoic acid (LA) or lipol (LOH), have been designed and synthesized to protect the skin against oxidative damage due to UVR. These co-drugs and their parent compounds, alone and in combination, were evaluated for their AO potential in skin exposed to ferrous sulfate (FeSO4) or UVR and evaluated for lipid peroxidation using the thiobarbituric acid reactive substance (TBARS) assay. The measurement of lipid peroxidation was determined by the formation of the end product, malondialdehyde (MDA). The experiments performed were aimed at confirming that the co-drugs, when hydrolyzed to TOC and LA or LOH, showed potent activity that is enhanced by the simultaneous availability of both TOC and LA/LOH. Further experiments were carried out using UVR on intact skin to induce lipid peroxidation. Penetration and hydrolysis of TOCE and TOCC was estimated in the epidermal (ED) layer of the intact skin using Franz diffusion cells and high-performance liquid chromatography (HPLC) was used to quantify the co-drugs and the parent compounds in skin layers. Hydrolysis of the co-drugs was evaluated based on release of TOC from the co-drugs, since transformation to the parent compounds via hydrolysis is an integral part of the activity of the co-drugs. Subsequently, the TBARS assay was carried out on treated skin to determine if the amount of co-drug penetrating into the viable layers of the skin was sufficient to inhibit lipid peroxidation. The parent compounds of the ester co-drugs (\316\261-TOC+LA; \316\264-TOC+LA) and the carbonate co-drugs (\316\261-TOC+LOH; \316\264-TOC+LOH) exhibited significant synergistic antioxidant activity across the concentration ranges evaluated. Antioxidant activity of the co-drugs (TOCE and TOCC) was observed but was dependent on the extent of hydrolysis. Greater hydrolysis of the co-drugs correlated with higher AO activity. The \316\264-analogues hydrolyzed to a greater extent than the \316\261-co-drugs on exposure to UVR. The penetration and hydrolysis of co-drugs in the ED layer was comparable to the observed AO activity. The presented data suggest that these topical co-drugs can serve as potent inhibitors of lipid peroxidation in the skin.
Citation
Sodvadia R. Antioxidant activity of \316\261- and \316\264-tocopheryl ester and carbonate co-drugs on UV-induced lipid peroxidation in skin [thesis]. Ann Arbor (MI): Proquest LLC; 2014. 77 p.
ACPHS Research Commons URI
Description
Click on the Resource Link to find this item in the ACPHS Library catalog.