To report a novel method using immobilized DNA within mesh to sequester drugs that have intrinsic DNA binding characteristics directly from flowing blood. DNA binding experiments were carried out in vitro with doxorubicin in saline (PBS solution), porcine serum, and porcine blood. Genomic DNA was used to identify the concentration of DNA that shows optimum binding clearance of doxorubicin from solution. Doxorubicin binding kinetics by DNA enclosed within porous mesh bags was evaluated. Flow model simulating blood flow in the inferior vena cava was used to determine in vitro binding kinetics between doxorubicin and DNA. The kinetics of doxorubicin binding to free DNA is dose-dependent and rapid, with 82–96 % decrease in drug concentration from physiologic solutions within 1 min of reaction time. DNA demonstrates faster binding kinetics by doxorubicin as compared to polystyrene resins that use an ion exchange mechanism. DNA contained within mesh yields an approximately 70 % decrease in doxorubicin concentration from solution within 5 min. In the IVC flow model, there is a 70 % drop in doxorubicin concentration at 60 min. A DNA-containing ChemoFilter device can rapidly clear clinical doses of doxorubicin from a flow model in simple and complex physiological solutions, thereby suggesting a novel approach to reduce the toxicity of DNA-binding drugs.
Purpose
To establish that a magnetic device designed for intravascular use can bind small iron particles in physiologic flow models.
Materials and Methods
Uncoated iron oxide particles 50–100 nm and 1–5 μm in size were tested in a water flow chamber over a period of 10 minutes without a magnet (ie, control) and with large and small prototype magnets. These same particles and 1-μm carboxylic acid–coated iron oxide beads were likewise tested in a serum flow chamber model without a magnet (ie, control) and with the small prototype magnet.
Results
Particles were successfully captured from solution. Particle concentrations in solution decreased in all experiments (P < .05 vs matched control runs). At 10 minutes, concentrations were 98% (50–100-nm particles in water with a large magnet), 97% (50–100-nm particles in water with a small magnet), 99% (1–5-μm particles in water with a large magnet), 99% (1–5-μm particles in water with a small magnet), 95% (50–100-nm particles in serum with a small magnet), 92% (1–5-μm particles in serum with a small magnet), and 75% (1-μm coated beads in serum with a small magnet) lower compared with matched control runs.
Conclusions
This study demonstrates the concept of magnetic capture of small iron oxide particles in physiologic flow models by using a small wire-mounted magnetic filter designed for intravascular use.
To computationally optimize the design of an endovascular magnetic filtration device that binds iron oxide nanoparticles and to validate simulations with experimental results of prototype devices in physiologic flow testing. Three-dimensional computational models of different endovascular magnetic filter devices assessed magnetic particle capture. We simulated a series of cylindrical neodymium N52 magnets and capture of 1500 iron oxide nanoparticles infused in a simulated 14 mm-diameter vessel. Device parameters varied included: magnetization orientation (across the diameter, “D”, along the length, “L”, of the filter), magnet outer diameter (3, 4, 5 mm), magnet length (5, 10 mm), and spacing between magnets (1, 3 mm). Top designs were tested in vitro using 89Zr-radiolabeled iron oxide nanoparticles and gamma counting both in continuous and multiple pass flow model. Computationally, “D” magnetized devices had greater capture than “L” magnetized devices. Increasing outer diameter of magnets increased particle capture as follows: “D” designs, 3 mm: 12.8–13.6 %, 4 mm: 16.6–17.6 %, 5 mm: 21.8–24.6 %; “L” designs, 3 mm: 5.6–10 %, 4 mm: 9.4–15.8 %, 5 mm: 14.8–21.2 %. In vitro, while there was significant capture by all device designs, with most capturing 87–93 % within the first two minutes, compared to control non-magnetic devices, there was no significant difference in particle capture with the parameters varied. The computational study predicts that endovascular magnetic filters demonstrate maximum particle capture with “D” magnetization. In vitro flow testing demonstrated no difference in capture with varied parameters. Clinically, “D” magnetized devices would be most practical, sized as large as possible without causing intravascular flow obstruction.
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