Cannabinoid encapsulating nanoparticles for atherosclerosis therapy

Abstract

Atherosclerosis, the chronic inflammation of the arterial wall, is one of the leading causes of death in the western societies. Which is characterized by the accumulation of inflammatory macrophages and necrotic regions in the intima. Rupture of the plaque can lead to thrombosis, a blood clot in the blood vessel, blocking the natural flow of the blood. If left untreated the entire lumen can be blocked and the results can be fatal. Progression in atherosclerosis is mainly driven by the build up of macrophages. An important phenotype on these cells are cannabinoid receptors, important in the control of inflammatory pathways. By presenting inflammatory relieving cannabinoids to these receptors, the macrophages could become less inflammatory. A localized delivery would give the additional benefit of reducing systematic side effects. High density lipoprotein based nanoparticles have shown to be great carriers for drug molecules. Additionally, high density lipoproteins are able to relieve AS up to a certain extend. In this research we analyzed physical and physio-chemical properties of different nanoparticle formulations. Specifically, the size, morphology and ζ-potential. Next we investigated the cannabinoid receptor expression on different types of macrophages, which verified that macrophages in atherosclerotic conditions have an abundance of our target receptor. Finally we performed a small in vitro study showing both empty and cannabinoid loaded nanoparticles relieved pro-inflammatory signals.