Folate targeted glutathione antioxidant delivery systems and their impact on intracellular oxidative status

POLY 497

Benjamin S. Lepene, blepene@vt.edu1, Sharlene R. Williams2, Timothy E. Long, telong@vt.edu2, and Craig D. Thatcher, cthatche@vt.edu3. (1) Department of Biomedical and Veterinary Sciences, Virginia Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Duck Pond Drive, Blacksburg, VA 24061, (2) Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, (3) Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA 24061
Production of reactive oxygen species (ROS) and the resulting cellular oxidative damage occurs in a wide range of inflammatory disease conditions. Monocyte recruitment and formation of activated macrophages over-expressing folate receptors (FR) are well-known events in the pro-inflammatory process. Folate-linked therapeutic compounds, such as antioxidants (AOX), can be utilized for active targeting of macrophages. The objectives of the current study include (1) the synthesis of a nanoscale macromolecular based AOX delivery system exhibiting active targeting and pH-responsive release, (2) Characterization of the active targeting ability and cytotoxicity response of the synthesized delivery system, and (3) the ability of the AOX system to scavenge free radicals in an in-vitro cell culture system. A murine macrophage cell line (RAW 264.7) was used to investigate the synthesized AOX delivery systems ability to target activated macrophages expressing FR as well as to assess the delivery system's ability to limit cellular oxidative damage.