Description:

Presenter: Neel Mansukhani, MD

Atherosclerosis is the leading cause of death and disability in the United States. However, best medical therapy still results in a high rate of death or major adverse cardiovascular events. The purpose of this work is to develop a targeted nanofiber based therapy for the treatment of atherosclerosis. Atherosclerosis is studied using the LDL receptor knockout mouse model. We have developed a self-assembling peptide amphiphile (PA) nanofiber which uses an apoA1 mimetic sequence to target areas of atherosclerosis. In vitro, we designed and synthesized PA nanofibers, confirmed self assembly of the PA and nanofiber formation, and incorporated a therapeutic for targeted delivery by the PA nanofiber to areas of atherosclerosis. In vivo, we have confirmed PA binding efficacy and duration at areas of atherosclerosis, determined optimum dose and concentration of the PA for intravenous injection, and have completed biodistribution and pharmacokinetic studies of the PA. Finally, we have completed a pilot treatment study of atherosclerosis using the PA to ensure feasibility. A long-term treatment study for atherosclerosis using the targeted PA nanofiber which we have developed is currently in progress.