Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part II: Arborizing Catheter for Convection-Enhanced Delivery in Tissue Phantoms

ABSTRACT

Convection-enhanced delivery (CED) is the process of local, pressure driven flow of drugs into brain parenchyma containing tumor tissue, resulting in greater distribution of the infused drugs compared to diffusion-dependent therapies. Nevertheless, even with the advantage of CED over simple diffusion, the large volumes necessary to target entire tumors and peritumor volumes have been previously unachievable with currently available catheters. We present a novel, multiport, arborizing catheter designed specifically for improving drug distribution into the brain. We evaluated the performance of the arborizing catheter by quantifying volume dispersed (V_d) and mean distribution ratios (V_d:V_i) in infusion studies using agarose brain phantoms and compared results to a single-port catheter. Three experimental groups were evaluated: (i) single-port infusions at 1 μL/min; (ii) single-port infusions at 7 μL/min; and (iii) seven-port arborizing catheter infusions at 1 μL/min/port. Significantly greater V_d was calculated for the arborizing catheter group (10.47 ± 1.07 cm³) compared with the single-port catheter groups at the low- and high-flow rates (2.36 ± 0.21 cm³ and 5.14 ± 0.56 cm³), respectively. V_d:V_i for the arborizing catheter was 37% lower than the single-port catheter at 1 μL/min, but 100% greater than the single-port catheter at 7 μL/min. The multiport, arborizing catheter produced the greatest distribution of the infusate, which would be advantageous for CED; however, it did not exhibit the greatest distribution ratio, likely due to overlapping distribution volumes from the multiple individual ports.