Non-affinity factors modulating vascular targeting of nano- and microcarriers

Abstract

Particles capable of homing and adhering to specific vascular biomarkers have potential as fundamental tools in drug delivery for mediation of a wide variety of pathologies, including inflammation, thrombosis, and pulmonary disorders. The presentation of affinity ligands on the surface of a particle provides a means of targeting the particle to sites of therapeutic interest, but a host of other factors come into play in determining the targeting capacity of the particle. This review presents a summary of several key considerations in nano- and microparticle design that modulate targeted delivery without directly altering epitope-specific affinity. Namely, we describe the effect of factors in definition of the base carrier (including shape, size, and flexibility) on the capacity of carriers to access, adhere to, and integrate in target biological milieus. Furthermore, we present a summary of fundamental dynamics of carrier behavior in circulation, taking into account interactions with cells in circulation and the role of hemodynamics in mediating the direction of carriers to target sites. Finally, we note non-affinity aspects to uptake and intracellular trafficking of carriers in target cells. In total, recent findings presented here may offer an opportunity to capitalize on mitigating factors in the behavior of ligand-targeted carriers in order to optimize targeting.

Effects of the Microparticle Shape on Cellular Uptake

“…The properties of nano/micro particles also play an important role in cell adhesion which is the first step to endocytosis of particles 2, 3 . The physical properties (size and shape), surface properties (charge and hydrophilicity), and mechanical properties (stiffness) of particles are all known to affect endocytosis 4–7 . Exploring and understanding the relationships between particle properties and endocytosis can increase the efficiency of drugs entering cancer cells by improving the particle design.…”

Red blood cells: Supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems

“…Indeed, RBCs normally occupy ~50% of blood volume and, due to such high concentration and peculiar hemodynamics, greatly influence circulation of other particles and their interaction with vascular walls [112]. In arteries, where blood perfusion is associated with high levels of fluid shear stress, RBCs tend to occupy the mainstream and avoid the micron-scale marginal layer of blood that directly contacts endothelial surface, thereby pushing other circulating particles to the cell-free layer (Fig.…”

“…The amplitude of margination effect depends on a variety of factors including hydrodynamic conditions, vessel diameter and shape, and geometry of particles [112,118–120]. Here, we will focus on the role that circulating RBCs, either alone or interplayed with the above factors, have on influencing particle margination.…”

Unintended effects of drug carriers: Big issues of small particles

“…Similarly, nanoparticle is also different from bulk materials. A common diameter size range for NPs injected systemically is 50–300 nm [58]. Enhanced surface/mass (S/M) ratio in NPs compared to larger counterparts exerts significant impact on their circulation, degradation, and intracellular delivery (Table 1).…”