(598b) Engineering Lipid Nanoparticles for Targeting Inflammation Site in Atherosclerosis

Atherosclerosis is an arterial disease characterized by the formation of plaques composed of cholesterol and macrophages. Low density lipoprotein (LDL) particles get attached to the proteoglycan of endothelium inside artery and become highly susceptible to oxidation and other chemical modifications. Oxidized LDLs induce inflammation by increasing the leukocyte adhesiveness and permeability to the endothelium. This condition may lead to further complications such coronary heart disease and myocardial infarction which are leading causes of death in the developing world. Targeted delivery of drugs to the diseased tissue can be efficient method in treatment of atherosclerotic plaque. It has several advantages as compared to systemic drug delivery such as reduced dosage of drug, lesser side effects, decrease in cost of therapy and increased accumulation of drug within the target tissue. Vitamin E is known for its antioxidant properties and can play a vital role in treatment of atherosclerosis.

In this study we plan to develop vitamin E loaded lipid nanoparticles (LNPs) targeting the inflammation site in atherosclerosis. The fluorescently tagged lipid nanoparticles were engineered using several phospholipids and were crosslinked with Hyaluronic acid (HALNPs). The reactive oxidation species (ROS) studies was performed using stem cells where oxidative stress was created using peroxide (H2O2) and then the vitamin E loaded lipid nanoparticles were targeted to these cells. These nanoparticles were also delivered to 3D co-culture of smooth muscle cells (SMC) and endothelial cells (EC) to study the trafficking and specific targeting. We observed that the targeted delivery of HALNPs loaded with vitamin E significantly decreased the oxidative stress induced in stem cells due to peroxide. We further plan to perform ex-vivo HALNP delivery experiments using arteries extracted from pig.