Augmenting convection-enhanced delivery through simultaneous co-delivery of fluids and laser energy with a fiberoptic microneedle device

Abstract

Abstract This paper describes a new infusion catheter, based on our fiberoptic microneedle device (FMD), designed with the objective of photothermally augmenting the volumetric dispersal of infused therapeutics. We hypothesize that concurrent delivery of laser energy, causing mild localized photothermal heating (4-5 °C), will increase the spatial dispersal of infused chemotherapy over a long infusion period. Agarose brain phantoms, which mimic the brain’s mechanical and fluid conduction properties, were constructed from 0.6 wt% Agarose in aqueous solution. FMDs were fabricated by adhering a multimode fiberoptic to a silica capillary tube, such that their flat-polished tips co-terminated. Continuous-wave 1064 nm light was delivered simultaneously with FD&C Blue #2 (5%) dye into phantoms. Preliminary experiments, where co-delivery was tested against fluid delivery alone (through symmetrical infusions into in vivo rodent models), were also conducted. In the Agarose phantoms, volumetric dispersal was demonstrated to increase by more than 3-fold over a four-hour infusion time frame for co-delivery relative to infusion-only controls. Both forward and backward (reflux) infusions were also observed to increase slightly. Increased volumetric dispersal was demonstrated with co-delivery in an in vivo rodent model. Photothermal augmentation of infusion was demonstrated to influence the directionality and increase the volume of dye dispersal in Agarose brain phantoms. With further development, FMDs may enable a greater distribution of chemotherapeutic agents during CED therapy of brain tumors. Keywords: convection-enhanced delivery, fiberoptics, malignant glioma, simultaneous co-delivery, photothermal, minimally-invasive, chemotherapy, micorneedles