Walker Department of Mechanical Engineering, University of Texas at Austin, 204 E. Dean Keeton Street, Stop C2200, Austin, TX, 78712-1591.
Department of Biomedical Engineering, University of Texas at Austin, 301 E. Dean Keeton St. C2100, Austin, TX, 78712-2100.
J Biomech Eng. 2022 Nov 1;144(11). doi: 10.1115/1.4054729.
Convection-enhanced delivery (CED) has been extensively studied for drug delivery to the brain due to its inherent ability to bypass the blood-brain barrier. Unfortunately, CED has also been shown to inadequately distribute therapeutic agents over a large enough targeted tissue volume to be clinically beneficial. In this study, we explore the use of constant pressure infusions in addition to controlled catheter movement as a means to increase volume dispersed (Vd) in an agarose gel brain tissue phantom. Constant flow rate and constant pressure infusions were conducted with a stationary catheter, a catheter retracting at a rate of 0.25 mm/min, and a catheter retracting at a rate of 0.5 mm/min. The 0.25 mm/min and 0.5 mm/min retracting constant pressure catheters resulted in significantly larger Vd compared to any other group, with a 105% increase and a 155% increase compared to the stationary constant flow rate catheter, respectively. These same constant pressure retracting infusions resulted in a 42% and 45% increase in Vd compared to their constant flow rate counterparts. Using constant pressure infusions coupled with controlled catheter movement appears to have a beneficial effect on Vd in agarose gel. Furthermore, constant pressure infusions reveal the fundamental limitation of flow-driven infusions in both controlled catheter movement protocols as well as in stationary protocols where maximum infusion volume can never be reliably obtained.
由于能够绕过血脑屏障， 注射增强输送（CED）已被广泛研究用于将药物输送到大脑。 不幸的是，CED 也被证明无法将治疗剂充分分布到足够大的靶向组织体积中，从而具有临床益处。 在这项研究中，我们探讨了在控制导管运动的同时使用恒压输注作为增加琼脂糖凝胶脑组织模型中分散体积（Vd）的方法。 恒流率和恒压输注是在固定导管、以 0.25mm/min 的速度缩回的导管和以 0.5mm/min 的速度缩回的导管上进行的。0.25mm/min 和 0.5mm/min 缩回的恒压导管与其他任何组相比，Vd 显著增加，与固定流速导管相比，分别增加了 105%和 155%。与恒流率导管相比，相同的恒压缩回输注使 Vd 增加了 42%和 45%。使用恒压输注结合控制导管运动似乎对琼脂糖凝胶中的 Vd 具有有益的影响。 此外，恒压输注揭示了流动驱动输注在控制导管运动协议以及固定协议中的基本局限性，在这些协议中，最大输注体积永远无法可靠获得。
