(286) In vivo metabolism of cholesterol-containing nanoparticles generates immune modulatory oxysterols
Introduction: Endogenous nanometer-scale lipid particles undergo cholesterol metabolism in macrophages, generating oxidized cholesterol products (oxysterols) that are potent immune modulators associated with certain malignancies.[1] Given that the majority of clinically approved nanoparticle drugs are lipid nanoparticles (LNPs) containing cholesterol, and macrophages play a major role in LNP uptake, it is likely that LNP-associated cholesterol is metabolized by similar oxidation pathways, explaining their immune modulatory effects. Our goal is to elucidate the metabolic pathways of LNP's cholesterol.
Learning Objectives:
Determine the metabolic fate of LNP-associated cholesterol in vitro and in vivo.
Evaluate the production of oxysterols from liposomes in macrophages and different body tissues.
Understand the implication of cholesterol metabolites on immune response.
Shadan Modaresahmadi, PharmD – PhD candidate, Texas Tech University Health Sciences Center; Indhumathy Subramaniyan, MS – Sr Research Scientist, Texas Tech University Health Sciences Center; Vindhya Edpuganti, PhD – Senior Research Scientist, Texas Tech University Health Sciences Center; Jalpa Patel, BS in Pharmacy – Lead Technician, Texas Tech University Health Sciences Center; Md. Rakibul Islam, PhD – Post Doctoral Research Associate, Texas Tech University Health Sciences Center; William Putnam, PhD – Professor, Texas Tech University Health Sciences Center; Ninh La-Beck, PharmD – Associate Professor, Texas Tech University Health Sciences Center