The effects of particle size, shape, density and flow characteristics on particle margination to vascular walls in cardiovascular diseases

Abstract

Introduction: Vascular-targeted drug delivery is a promising approach for the treatment of atherosclerosis, due to the vast involvement of endothelium in the initiation and growth of plaque, a characteristic of atherosclerosis. One of the major challenges in carrier design for targeting cardiovascular diseases (CVD) is that carriers must be able to navigate the circulation system and efficiently marginate to the endothelium in order to interact with the target receptors. Areas covered: This review draws on studies that have focused on the role of particle size, shape, and density (along with flow hemodynamics and hemorheology) on the localization of the particles to activated endothelial cell surfaces and vascular walls under different flow conditions, especially those relevant to atherosclerosis. Expert opinion: Generally, the size, shape, and density of a particle affect its adhesion to vascular walls synergistically, and these three factors should be considered simultaneously when designing an optimal carrier for targeting CVD. Available preliminary data should encourage more studies to be conducted to investigate the use of nano-constructs, characterized by a sub-micrometer size, a non-spherical shape, and a high material density to maximize vascular wall margination and minimize capillary entrapment, as carriers for targeting CVD. ARTICLE HISTORY

Comparative in vitro transportation of pentamidine across the blood-brain barrier using polycaprolactone nanoparticles and phosphatidylcholine liposomes

“…Spherical shaped or spheres are ease to synthesis and have been studied for years. They are quickly up taken by microphages and stay for shorter time in circulation as compared to non-spherical nanoparticles [25,26]. However, the sizes observed also correlated well with the hydrodynamic diameters measured by the Zetasizer (Figure 4).…”

Elucidating the Influences of Size, Surface Chemistry, and Dynamic Flow on Cellular Association of Nanoparticles Made by Polymerization‐Induced Self‐Assembly

“…Confocal microscopy images in Figure showed that large nanoparticles (130 nm) associated with HUVECs to a greater extent than medium and small particles (70 and 40 nm), which is consistent with data obtained by flow cytometry (Figure ). It has been shown that large nanoparticles exhibit a higher tendency to tumble out of the general circulation and scavenge along vascular walls than smaller nanomaterials . This tendency may increase the exposure of large nanoparticles with TA‐tagged groups to endothelial cells and as a result, increase cellular association.…”

“…For the above clinical applications, nanomaterials circulate in the human vascular network before reaching their targets (e.g., cancer cells, immune cells, or blood clots) . As such, investigating and understanding the complex nano–bio interactions between nanomaterials and biological systems inside vascular networks (e.g., endothelial cell adhesion) are critical for designing nanoparticles with desired properties for these applications . For instance, nanoparticles carrying anticancer drugs are expected to have a minimal off‐target association with healthy endothelial cells before reaching tumors .…”

“…For instance, nanoparticles carrying anticancer drugs are expected to have a minimal off‐target association with healthy endothelial cells before reaching tumors . On the other hand, specific association between nanomaterials and endothelial cells may be beneficial for use in cardiovascular diseases . Despite these potential benefits, the interactions between nanomaterials and endothelial cells under flow conditions in vascular networks remain poorly characterized due to a lack of suitable models …”

Controlling Nanomaterial Size and Shape for Biomedical Applications via Polymerization‐Induced Self‐Assembly

“…Both the size and shape of nanoparticles are crucial factors that impact their properties and applications . For instance, the size and shape of PISA nanoparticles have been found to significantly affect their in vivo biodistribution .…”