1. Fiberoptic microneedle device facilitates volumetric infusate dispersion during convection-enhanced delivery in the brain.
- Author
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Hood RL, Andriani RT Jr, Emch S, Robertson JL, Rylander CG, and Rossmeisl JH Jr
- Subjects
- Animals, Cerebrum, Coloring Agents administration & dosage, Craniotomy, Drug Delivery Systems methods, Evans Blue administration & dosage, Evans Blue pharmacokinetics, Gadolinium administration & dosage, Gadolinium pharmacokinetics, Hyperthermia, Induced instrumentation, Infusions, Intraventricular, Liposomes, Magnetic Resonance Imaging, Male, Rats, Rats, Inbred F344, Rhodamines administration & dosage, Rhodamines pharmacokinetics, Serum Albumin administration & dosage, Serum Albumin pharmacokinetics, Coloring Agents pharmacokinetics, Convection, Drug Delivery Systems instrumentation, Hyperthermia, Induced methods, Lasers, Needles, Optical Fibers
- Abstract
Background and Objectives: A fiberoptic microneedle device (FMD) was designed and fabricated for the purpose of enhancing the volumetric dispersal of macromolecules delivered to the brain through convection-enhanced delivery (CED) by concurrent delivery of sub-lethal photothermal hyperthermia. This study's objective was to demonstrate enhanced dispersal of fluid tracer molecules through co-delivery of 1,064 nm laser energy in an in vivo rodent model., Materials and Methods: FMDs capable of co-delivering fluids and laser energy through a single light-guiding capillary tube were fabricated. FMDs were stereotactically inserted symmetrically into both cerebral hemispheres of 16 anesthetized rats to a depth of 1.5 mm. Laser irradiation (1,064 nm) at 0 (control), 100, and 200 mW was administered concurrently with CED infusions of liposomal rhodamine (LR) or gadolinium-Evans blue-serum albumin conjugated complex (Gd-EBA) at a flow rate of 0.1 µl/min for 1 hour. Line pressures were monitored during the infusions. Rodents were sacrificed immediately following infusion and their brains were harvested, frozen, and serially cryosectioned for histopathologic and volumetric analyses., Results: Analysis by ANOVA methods demonstrated that co-delivery enhanced volumetric dispersal significantly, with measured volumes of 15.8 ± 0.6 mm(3) for 100 mW compared to 10.0 ± 0.4 mm(3) for its fluid only control and 18.0 ± 0.3 mm(3) for 200 mW compared to 10.3 ± 0.7 mm(3) for its fluid only control. Brains treated with 200 mW co-delivery exhibited thermal lesions, while 100 mW co-deliveries were associated with preservation of brain cytoarchitecture., Conclusion: Both lethal and sub-lethal photothermal hyperthermia substantially increase the rate of volumetric dispersal in a 1 hour CED infusion. This suggests that the FMD co-delivery method could reduce infusion times and the number of catheter insertions into the brain during CED procedures., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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