An anti-inflammatory Glyburide-loaded nanoghost for atherosclerosis therapy: A red blood cell based bio-mimetic strategy

Abstract

Inflammation control is becoming a critical strategy for atherosclerosis management, because inflammation is involved in plaque progression. In this regard, a biomimetic strategy using cell membrane-coated nanoparticles has some promising advantages. In the study, a RBC membrane-based nanoghost containing Glyburide (Glibenclamide) was prepared using an extrusion method. The hydrodynamic size and zeta potential of the nanoghost were changed compared to PLGA nanoparticles. In addition, a nanoghost with a diameter and shell size of 125 nm and 8.3 nm was obtained based on the TEM measurement. The fabricated nanoghost was not only hemocompatible but also was biocompatible, showing no significant induction of apoptosis. According to RT-PCR assay, the expression levels of inflammatory genes including NLRP3, IL-1β, IL-18 caspase1, 8 and 9 were decreased. In accordance with in vitro anti-inflammation properties, total foam cells, total surface area in tunica intima and population of CD14+ cells were decreased in the rabbit model of atherosclerosis upon nanoghost treatment, compared to positive control. Furthermore, macrophages in aorta sections exhibited M1 to M2 polarization. In general, the development of Glyburide-loaded nanoghost can be considered as a potential therapeutic for controlling the progression and inflammation of atherosclerotic plaque.