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Oral PresentationPolymerized HDLs for vaccine deliveryFrances Acevedo MarianiGwangseong Kim, Dept of Pharmaceutical Sciences, University of MichiganAdvisor: Anna Schwendeman, Dept. of Medicinal Chemistry, University of MichiganHigh-density lipoprotein (HDL) is a natural nanoparticle composed phospholipid bilayer andApolipoprotein A-I (ApoA-I). The main functions of HDL are to efflux the excess of cholesterolfrom endothelial cells and transport it to the liver for elimination. Due to their size (8-10 nm) andlong circulation half-life (1-3 days) they could be used for intravenous delivery of peptideantigens covalently bound to HDL phospholipids. Unfortunately HDL undergoes rapidremodeling in plasma by exchanging phospholipids with other membranes, and potentiallyloosing phospholipid bound surface antigens. Polymerization of HDL lipid bilayer will likelyprevent plasma remodeling. ApoAI mimetic peptide (5A) was complexed with polymerizablelipid, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (Diyne PC), andsphingomyelin (SM) to form sHDL nanoparticles. Diyne PC, SM and 5A were dissolved inorganic solvent, combined at 2:0:1, 1:1:1, 0.5:1.5:1 and 0.25:1.75:1 weight ratios andlyophilized. The powders were hydrated to form HDLs and polymerized by UV light exposurefor 2 hours. The resulting sHDLs were analyzed to determine size (DLS), purity (gelchromatography – GPC), presence of liposome impurity (turbidity) and stability after cooling to4°C. Only polymerized HDLs composed exclusively of Diyne PC (2:0:1) remained intact, whilethe increase in impurities was observed for all other preparations. To increase purity andoptimize size, HDL were prepared at 1:0.5, 1:0.75, 1:1, 1:1.5 and 1:2 wt/wt ratios of 5A to DiynePC. The HDL purity increased with decrease of lipid content and stability was improved bypolymerization. The polymerized HDLs were prepared and their composition was optimized toachieve size characteristic size of 8-10 nm and physical stability. The polymerized HDL could bepotentially used for vaccine antigen delivery.15