Development of a Fiberoptic Microneedle Device for Simultaneous Co-Delivery of Fluid Agents and Laser Light with Specific Applications in the Treatment of Brain and Bladder Cancers
Hood, Robert Lyle
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This dissertation describes the development of the fiberoptic microneedle device (FMD), a microneedle technology platform for fluid and light delivery, from general engineering characterization to specific applications in treating bladder and brain cancers. The central concept of the FMD is physical modification of silica fiberoptics and capillary tubes into sharp microneedles capable of penetrating a tissue's surface, enabling light and fluid delivery into the interstitial spaces. Initial studies sought to characterize the mechanical penetration and optical delivery of multimode fiberoptics and capillary tubes modified through a custom, CO2 laser melt-drawing technique. Additional work with multimode fibers investigated using an elastomeric lateral support medium to ensure robust penetration of small diameter fibers. These early experiments laid an engineering foundation for understanding the FMD technology. Subsequent studies focused on developing the FMD to treat specific diseases. The first such investigation sought to leverage the high aspect ratio nature of FMDs made from long capillary tubes as a therapy delivery device deployable through the instrument channel of a urological cystoscope. The therapeutic strategy was to infuse single-walled carbon nanohorns (SWNHs), a carbon-based nanoparticle allowing surface modification and drug encapsulation, into the infiltrating front of later stage bladder tumors. The SWNHs primarily serve as exogenous chromophores, enabling a fluid-based control of photothermal heat generation created when the SWNHs interacted with laser energy from an interstitial FMD or a light-emitting fiber in the bladder's interior. The study described here primarily sought to characterize the dispersal of the infused SWNHs and the photothermal response of the particles when heated with a 1064 nm laser. The FMD was also developed as a platform capable of conducting convection-enhanced delivery (CED), a therapeutic approach to treat invasive tumors of the central nervous system such as malignant glioma (MG). Intracranial CED involves the placement of small catheters local to the tumor site and slow infusion of a chemotherapeutic over long timeframes (12-72 hours). A primary challenge of this treatment approach is infused chemotherapeutics not dispersing sufficiently to reach the infiltrating cells in the tumor's margins. The hypothetical improvement provided by the FMD technology is using sub-lethal photothermal heating to sufficiently increase the diffusive and convective transport of an infusate to reach infiltrative cells in the tumor's periphery. Initial experiments sought to demonstrate and characterize a heat-mediated increase of volumetric dispersal in Agarose tissue phantoms and ex vivo tissue. Subsequent studies with in vivo rodent models determined the best laser parameters to achieve the desired levels of diffuse, sub-lethal heat generation and then demonstrated the hypothesis of increasing the rate of volumetric dispersal though concurrent local hyperthermia. This research was the first demonstration of photothermal augmentation of an interstitially infused fluid's dispersal rate, which may have uses outside of the CED approach to brain cancer exhibited here. Taken in sum, this manuscript describes the potency and versatility of the FMD technology platform through its development in various biomedical applications.
- Doctoral Dissertations