Characterization of nanoparticle delivery in microcirculation using a microfluidic device

Abstract

This work focuses on the characterization of particle delivery in microcirculation through a microfluidic device. In microvasculature the vessel size is comparable to that of red blood cells (RBCs) and the existence of blood cells largely influences the dispersion and binding distribution of drug loaded particles. The geometry of the microvasculature leads to non-uniform particle distribution and affects the particle binding characteristics. We perform an in vitro study in a microfluidic chip with micro vessel mimicking channels having a rectangular cross section. Various factors that influence particle distribution and delivery such as the vessel geometry, shear rate, blood cells, particle size, particle antibody density are considered in this study. Around 10% higher particle binding density is observed at bifurcation regions of the mimetic microvasculature geometry compared to straight regions. Particle binding density is found to decrease with increased shear rates. RBCs enhance particle binding for both 210 nm and 2 μm particles for shear rates between 200-1600 s−1 studied. The particle binding density increases about 2-3 times and 6-10 times when flowing in whole blood at 25% RBC concentration compared to the pure particle case, for 210 nm and 2 μm particles respectively. With RBCs, the binding enhancement is more significant for 2 μm particles than that for 210 nm particles, which indicates an enhanced size dependent exclusion of 2 μm particles from the channel centre to the cell free layer (CFL). Increased particle antibody coating density leads to higher particle binding density for both 210 nm and 2 μm particles.

Biomimetic channel modeling local vascular dynamics of pro-inflammatory endothelial changes

“…This increased binding density of particles with higher antibody coating is consistent with other studies and our previous work. 21,48,49 Previous studies have reported the binding kinetics of particles with higher anti-ICAM-1 coating density to be significantly faster, 48,50 which could be valid for our study as our maximum particle flow time is only 6 min. The particle binding density decreased when the FSS increased from 6 to 12 dyn/cm 2 for both anti-ICAM-1 coating density cases.…”

“…An increase in FSS reduced the available time for particles to diffuse/marginate towards the endothelial cell surface, which reduced their binding density as observed in other studies. 48 The particle binding density also does not reduce for FSS > 12 dyn/ cm 2 ( Fig. 6).…”

“…Similar behavior has been reported in previous studies where it is observed that flow cannot generate enough drag force on the particle to significantly reduce the particle binding density after a critical shear rate. 48 Here, the receptor-ligand bond strength between the 210 nm particle and the ICAM-1 molecules expressed on the endothelial layer should be higher than the drag force produced by the FSS on the nanometer scale particle (drag force generated is proportional to the size of the particle).…”

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

“…In vitro work by Liu et al found that blood enhances both 210nm and 2µm polystyrene particle binding in microcirculation. The binding density increased threefold more for the 2µm particles compared to the 210nm particles [112]. Eniola-Adefeso et al examined the effect of particle size (500nm to 10µm) on margination propensity in blood and observed an increase in this phenomenon with increasing particle size [101,105].…”

Synthesis of copper nanocolloids using a continuous flow based microreactor

“…The advantages of microreactors are their high surface area to volume ratio, tunable inner-wall properties, versatile flow-orientation, and flexible-structural designs [13][14][15][16][17][18][19][20][21]. In addition, diffusive exchange of heat and mass can be achieved within small length scales.…”