Design and Validation of Medical Devices for Photothermally Augmented Treatments

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Date
2014-09-15
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Virginia Tech
Abstract

*1-Dimensional Advective-Diffusion Model in Porous Media

Infusion of therapeutic agents into tissue is makes use of two mass transport modes: advective transport, and molecular diffusion.

Bulk infusion into a 0.6% wt agarose phantom was modeled as an infinite, homogenous, and isotropic porous medium saturated with the same solvent used in the infused dye tracer. The source is assumed to be spherical and isotropic with constant flow rate and concentration. The Peclet numberdecreases with power function Pe = 15762t0.337 due to the decrease in mean dye-front pore velocity as V goes to Vfinal.

Diffusive mass transport does not become significant during any relevent time period.

*Arborizing Fiberoptic Microneedle Catheter

We have developed an arborizing catheter that allows multiple slender fused-silica CED cannulae to be deployed within a target volume of the brain via a single needle tract, and tested it in a widely accepted tissue phantom.

The arborizing catheter was constructed by bonding and encapsulating seven slender PEEK tubes in a radially symmetric bundle with a progressive helical angle along the length, then grinding a conicle tip where the helical angle is greatest.

The catheter was tested by casting 0.6% wt agarose around the device with all needles deployed to a tip-to-tip distance of 4 mm. Phantom temperature was maintained at 26 ± 2°C. 5% wt Indigo Carmine dye was infused at a rate of 0.3 uL/min/needle for 4 hours.

N=4 infusions showed a Vd/Vi of 139.774, with a standard deviation of 45.01. This is an order of magnitude greater than single-needle infusions under similar conditions [45]. The arborizer showed the additional benefit of arresting reflux propagating up the lengths of individual needles, which has historically been a weakness of single-needle CED catheter designs.

*In Vivo Co-Delivery of Single Walled Carbon Nano-horns and Laser Light to Treat Human Transitional Cell Carcinoma of the Urinary Bladder in a Rodent Model

Using a rodent model we explored a treatment method for Transitional Cell Carcinoma (TCC) in the urinary bladder in which Single Walled Carbon Nanohorn (SWNH) solution and 1064 nm laser light are delivered into tumorous tissue via a co-delivery Fiberoptic Microneedle Device (FMD).

Preliminary treatment parameters were determined by injecting SWNH solutions with concentrations of 0 mg/mL, 0.17 mg/mL, or 0.255 mg/mL into ex vivo porcine skin and irradiating each for three minutes at laser powers of 500 mW, or 1000 mW. The combination with the greatest temperature increase without burning the tissue, 0.17 mg/mL at 1000 mW, was selected for the in vivo treatment.

TCC tumors were induced in a rodent model by injecting a solution of 106 AY27 urothelial carcinoma cells into the lateral aspect of the left hind leg of young, female F344 rats. When tumors reached 5-10 mm3, rats were anesthitized and treated. SWNH solution was injected directly into the tumor and irradiated until the target temperature of 60degC was achieved. The rats were then recovered from anestesia and monitored for 7-14 days, at which point they were humanely sacrificed, and the tumors prepared for histological examination.

Histological assessment of areas of FMD treatment correlated well with gross morphological appearance. Foci of tumor necrosis showed sharp (1-2 mm) delineation from areas of viable tumor (not treated) and normal tissue.

We believe we have demonstrated the feasibility of using the FMD for treatment of urothelial carcinoma using an animal model of this disease, and are encouraged to continue development of this treatment and testing in larger animal models.

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Keywords
Convection-Enhanced Delivery, Carbon Nanohorn, Microneedle, Bladder, Transitional Cell Carcinoma, Malignant Glioma, Arborizing Catheter
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