Convection-enhanced delivery （CED） is a promising technique leveraging pressure-driven flow to increase penetration of infused drugs into interstitial spaces. We have developed a fiberoptic microneedle device for in...Convection-enhanced delivery （CED） is a promising technique leveraging pressure-driven flow to increase penetration of infused drugs into interstitial spaces. We have developed a fiberoptic microneedle device for inducing local sub-lethal hyperthermia to further improve CED drug distribution volumes, and this study seeks to quantitatively characterize this approach in agarose tissue phantoms. Infusions of dye were conducted in 0.6% （w/w） agarose tissue phantoms with isothermal conditions at 15 ℃, 20℃, 25 ℃, and 30 ℃. Infusion metrics were quantified using a custom shadowgraphy setup and image- processing algorithm. These data were used to build an empirical predictive temporal model of distribution volume as a function of phantom temperature. A second set of proof- of-concept experiments was conducted to evaluate a novel fiberoptic device capable of generating local photothermal heating during fluid infusion. The isothermal infusions showed a positive correlation between temperature and distribution volume, with the volume at 30℃ showing a 7-fold increase at 100 min over the 15 ℃ isothermal case. Infusions during photothermal heating （1064 nm at 500 mW） showed a similar effect with a 3.5-fold increase at 4 h over the control （0 mW）. These results and analyses serve to provide insight into and characterization of heat-mediated enhancement of volumetric dispersal.展开更多
基金the Coulter Foundation and NIH (NIH/NCI 1R21CA156078) for their funding of this project
文摘Convection-enhanced delivery （CED） is a promising technique leveraging pressure-driven flow to increase penetration of infused drugs into interstitial spaces. We have developed a fiberoptic microneedle device for inducing local sub-lethal hyperthermia to further improve CED drug distribution volumes, and this study seeks to quantitatively characterize this approach in agarose tissue phantoms. Infusions of dye were conducted in 0.6% （w/w） agarose tissue phantoms with isothermal conditions at 15 ℃, 20℃, 25 ℃, and 30 ℃. Infusion metrics were quantified using a custom shadowgraphy setup and image- processing algorithm. These data were used to build an empirical predictive temporal model of distribution volume as a function of phantom temperature. A second set of proof- of-concept experiments was conducted to evaluate a novel fiberoptic device capable of generating local photothermal heating during fluid infusion. The isothermal infusions showed a positive correlation between temperature and distribution volume, with the volume at 30℃ showing a 7-fold increase at 100 min over the 15 ℃ isothermal case. Infusions during photothermal heating （1064 nm at 500 mW） showed a similar effect with a 3.5-fold increase at 4 h over the control （0 mW）. These results and analyses serve to provide insight into and characterization of heat-mediated enhancement of volumetric dispersal.
