Recovery of Drug Delivery Nanoparticles from Human Plasma Using an Electrokinetic Platform Technology

Abstract

The effect of complex biological fluids on the surface and structure of nanoparticles is a rapidly expanding field of study. One of the challenges holding back this research is the difficulty of recovering therapeutic nanoparticles from biological samples due to their small size, low density, and stealth surface coatings. Here we present the first demonstration of the recovery and analysis of drug delivery nanoparticles from undiluted human plasma samples through the use of a new electrokinetic platform technology. The particles are recovered from plasma through a dielectrophoresis separation force that is created by innate differences in the dielectric properties between the unaltered nanoparticles and the surrounding plasma. We show this can be applied to a wide range of drug delivery nanoparticles of different morphologies and materials, including low density nano-liposomes. These recovered particles can then be analyzed using different methods including scanning electron microscopy to monitor surface and structural changes that result from plasma exposure. We believe that this new recovery technique is broadly applicable to the recovery of nanoparticles from high conductance fluids in a wide range of applications.

Electrokinetic device design and constraints for use in high conductance solutions

“…None of these solutions are ideal. This said, examples of commercial planar electrode arrays (Biological Dynamics, San Diego, CA), are seen in , which shows that this architecture has found success with high conductance solutions, and provides an empirical reference for further designs. Nevertheless, even these devices, designed to operate with high conductance solutions, have performance limitations due to adverse electrochemical effects when driven above recommended voltages or below recommended frequency of operation.…”

“…Electrokinetic separation devices offer tremendous promise in terms of miniaturization and direct separation of targeted biomarkers without the need to go through centrifugation, chemical isolation, and precipitation steps. New devices, which can operate under high conductance conditions (>0.5 S/m), have now been used to isolate cancer related cf‐DNA and drug delivery nanoparticles from un‐diluted blood and plasma samples. There is also research into using DEP to concentrate relevant biomarkers for chemical assay .…”

“…None of these solutions are ideal. This said, examples of commercial planar electrode arrays (Biological Dynamics, San Diego, CA), are seen in [2,4,5,[16][17][18][19], which shows that this architecture has found success with high conductance solutions, and provides an empirical reference for further designs. Nevertheless, even these devices, designed to operate with high Figure 1.…”

Emerging techniques in the isolation and characterization of extracellular vesicles and their roles in cancer diagnostics and prognostics

“…For example, the Heller group developed a dielectrophoretic method for the recovery of drug delivery nanoparticles as well as cancer related biomarkers from plasma and blood. 66,67 This approach can be used for the isolation and detection of EVs as well.…”

Entropy Generation on MHD Blood Flow of Nanofluid Due to Peristaltic Waves

“…He derived volumetric flow rate and pressure distribution and concluded that the wall shear stress and pressure drops are at a maximum at the throat of each stenosis and a minimum at the ends of each stenosis. Another important development in the history of bio-fluids is the investigation of nanoparticle separation technology which can be used to isolate a wide range of nanoparticles out of plasma with a minimum amount of manipulation [17]. This latest discovery enables researchers to study the mathematical modeling of drug delivery nanoparticle systems in blood flow.…”