Stewart Russell J, Sima Monika, Karz Jessica, Jones Joshua P
Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States.
Fluidx Medical Technology, Inc., Salt Lake City, UT, United States.
Front Bioeng Biotechnol. 2023 Jan 16;11:1095148. doi: 10.3389/fbioe.2023.1095148. eCollection 2023.
Endovascular embolization is a minimally invasive procedure during which blood flow to targeted tissues is selectively occluded. The list of clinical indications for embolization continues to expand. Liquid embolic agents are injectable compositions that transition into a solid or semi-solid form when introduced into blood vessels. The mechanism that triggers the liquid-to-solid transition is a key distinguishing feature of liquid embolic agents. GPX is a waterborne liquid embolic agent comprising oppositely charged polyelectrolytes: polyguanidinum and inorganic polyphoshate. solidification is driven by electrostatic condensation of the polyelectrolytes, triggered by ionic strength differentials. We report characterization of the material properties of GPX, it is effectiveness in acute animal studies, and its potential for chemoembolization. The viscosity of GPX can be varied over a wide range by adjusting the polyguanidinium MW and/or concentration. Formulation of GPX with either tantalum microparticles (30 wt%) or iodinated radiocontrast agents (300 mgI ml) did not significantly change the flow behavior of GPX; the viscosity was independent of shear rate and remained within a clinically practical range (80-160 cP). Formulation of GPX with doxorubicin substantially increased viscosity at low shear rates and resulted in a power law dependence on shear rate. High contrast and effective vascular occlusion were demonstrated in both swine kidneys and rete mirabile. Contrast from iodinated compounds was temporary, dissipating within hours. The doxorubicin release profile was linear over 90 days. The results demonstrate that GPX is a versatile liquid embolic platform that can be formulated with a wide range of viscosities injectable at clinically practical flow rates, with either transient or permanent contrast, and that can provide prolonged zero-order delivery of doxorubicin to embolized tissues.
血管内栓塞是一种微创手术，在此过程中，流向目标组织的血流被选择性阻断。栓塞的临床适应证列表在不断扩大。液体栓塞剂是一种可注射的组合物，当引入血管时会转变为固体或半固体形式。触发液固转变的机制是液体栓塞剂的一个关键区别特征。GPX是一种水性液体栓塞剂，由带相反电荷的聚电解质组成：聚胍和无机多磷酸盐。固化是由离子强度差异引发的聚电解质静电凝聚驱动的。我们报告了GPX材料特性的表征、其在急性动物研究中的有效性及其化学栓塞的潜力。通过调节聚胍的分子量和/或浓度，GPX的粘度可以在很宽的范围内变化。用钽微粒（30 wt%）或碘化放射性造影剂（300 mgI/ml）配制GPX不会显著改变GPX的流动行为；粘度与剪切速率无关，并且保持在临床实际范围内（80-160 cP）。用阿霉素配制GPX在低剪切速率下显著增加了粘度，并导致粘度与剪切速率呈幂律关系。在猪肾和奇静脉中均显示出高对比度和有效的血管闭塞。碘化化合物的对比度是暂时的，在数小时内消散。阿霉素的释放曲线在90天内呈线性。结果表明，GPX是一个多功能的液体栓塞平台，可以配制成具有各种粘度的制剂，以临床实际流速注射，具有短暂或永久的对比度，并且可以向栓塞组织提供阿霉素的长时间零级释放。
