Flow and adhesion of drug carriers in blood vessels depend on their shape: A study using model synthetic microvascular networks

Abstract

Development of novel carriers and optimization of their design parameters has led to significant advances in the field of targeted drug delivery. Since carrier shape has recently been recognized as an important design parameter for drug delivery, we sought to investigate how carrier shape influences their flow in the vasculature and their ability to target the diseased site. Idealized synthetic microvascular networks (SMNs) were used for this purpose since they closely mimic key physical aspects of real vasculature and at the same time offer practical advantages in terms of ease of use and direct observation of particle flow. The attachment propensities of surface functionalized spheres, elliptical/circular disks and rods with dimensions ranging from 1 µm to 20 µm were compared by flowing them through bifurcating SMNs. Particles of different geometries exhibited remarkably different adhesion propensities. Moreover, introduction of a bifurcation as opposed to the commonly used linear channel resulted in significantly different flow and adhesion behavior, which may have important implications in correlating these results to in vivo behavior. This study provides valuable information for design of carriers for targeted drug delivery.

Direct Tracking of Particles and Quantification of Margination in Blood Flow

“…This is in agreement with the findings from adhesion studies (3,(11)(12)(13)(14)17,18), as well as a recent direct-particle-tracking study by D'Apolito et al (7) in which two spherical particle sizes (1 mm and 3 mm) were investigated. It is conjectured that larger particles interact more readily with RBCs and, as a result of their frequent collisions with RBCs, are propelled toward the walls of a blood vessel sooner than smaller particles, which have less frequent interactions.…”

“…This so-called enhanced permeability and retention effect (8) further opens up the possibility of delivering chemotherapeutic drugs passively and more specifically to tumor sites, thereby limiting any damage to healthy tissues (9,10). A number of recent experimental (3,7,(11)(12)(13)(14)(15)(16)(17) and theoretical (18)(19)(20)(21)(22)(23) studies have suggested that particles of certain sizes and shapes have a higher margination propensity. This would facilitate the diffusion of these particles into tumor sites by allowing them to reach the leaky blood vessel walls and, ultimately, the tumors.…”

“…A number of experimental (3,7,(11)(12)(13)(14)(15)(16)(17) and theoretical (19,(21)(22)(23) studies have explored the effect of varying particle size on the margination propensity of particles. Several studies suggested that larger particles marginate much more readily than smaller particles, and that there is an optimal particle size for margination (3,12,14,15,19,22,23).…”

“…This work differs from previous studies in a number of ways. First, all previous experimental studies, with only two exceptions (7,38), assessed margination propensity based on the number density, or, more precisely, the fluorescence intensity, of fluorescent particles that adhered to the channel wall after a particle suspension and subsequently a buffer solution passed through the channel (3,(11)(12)(13)(14)(16)(17)(18)39). Although adhesion is related to margination, adhesion also depends on other factors such as hydrodynamic drag, the densities of ligands and receptors grafted onto the particle surface and the wall channel, the particle shape and contact orientation, and the particle size relative to the CFL (10,16,17,20,21).…”

Shear stress increases cytotoxicity and reduces transfection efficiency of liposomal gene delivery to CHO-S cells

“…Charoenphol et al showed that binding efficiency for spherical particles of size 100 nm to 10 lm increased with increasing particle size at a shear rate of 200 s -1 and for a given size the binding efficiency increased when the wall shear rate was increased from 200 to 1500 s -1 (Charoenphol et al 2010). In addition to size, particle shape affects the binding of particles under shear stress: adhesion of elongated and flattened particles was found to be significantly higher than spheres (Doshi et al 2010). This may be of relevance to the effectiveness in the presence of shear stress of carriers such as liposomes, which can deform in the presence of shear.…”