Abstract 18763: Characteristics and Anti-Atherosclerotic Properties of (-)-Epigallocatechin Gallate Loaded Lipid Nanoparticles in vitro

Abstract

BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of death and disability in the United States and other developed countries. Macrophages are major cells responsible for atherosclerotic lesion development. (-)-Epigallocatechin gallate (EGCG), a natural compound found in green tea, is valuable to prevent atherosclerosis. But EGCG’s low level of stability, bioavailability and targeting specificity in the body makes administering it in therapeutic doses unrealistic. METHODS AND RESULTS: We have successfully synthesized EGCG loaded lipid nanoparticles (ENP), which are composed of biocompatible and biodegradable lipids, surfactants and EGCG. The size of nanoparticles was less than 100 nm in diameter measured using a dynamic light scattering method and a transmission electron microscope. The encapsulation efficiency was around 90%. As compared to native EGCG, ENP significantly increased EGCG stability and macrophage EGCG content at 37°C. Remarkably, ENP significantly decreased human macrophage cholesteryl ester content measured using a high performance liquid chromatography (HPLC) system. ENP also significantly lowered both gene expression and protein secretion of monocyte chemoattractant protein 1 (MCP-1) in/from human macrophages measured using real-time PCR and ELISA assays, respectively. We also incorporated target ligands on the surface of ENP. The target ligands further increased the binding and uptake of those nanoparticles in human macrophages. CONCLUSIONS: ENP significantly enhanced EGCG stability, increased its cellular bioavailability, decreased cholesteryl ester content and MCP-1 expression in macrophages. Target ligands increased the target specificity of those nanoparticles to human macrophages. ENP with target ligands have a potential for preventing atherosclerotic lesion development through enhancing EGCG uptake by macrophages and decreasing macrophage cholesterol accumulation and inflammatory responses. Funding support: The project described was supported by Grant Number R15AT007013 from NIH NCCAM.