Ultrasound characterization of slow precipitating implants for vascular occlusion

A frequently utilized clinical treatment for liver cancer is the administration of drug eluting microspheres that embolize tumor vasculature depriving it of oxygen and nutrients. However, these beads are fairly large, leading to embolization far away from the tumor and reducing drug penetration. As an alternative, we have developed a slow precipitating in situ forming implant (ISFI) capable of deeper penetration and embolization, which we hypothesize will result in better treatment efficacy. In this study, ultrasound was utilized to determine precipitation kinetics of ISFI formulations formulated with varying solvent polarity and polymer molecular weight. Increasing polymer molecular weight from 15 kDa to 53 kDa led to a significant increase in precipitation rate after 5 minutes. A decrease in solvent polarity also led to a significantly higher precipitation rate, which was unexpected, but may be due to attenuation in polymer-rich and polymer-lean microdomains created with a low polar solvent. Tissue mimicking single channel phantoms were then used to determine occlusion distances. An increase in polymer molecular weight to 53kDa was the best formulation meeting both the aforementioned criteria. This study demonstrates, for the first time, ultrasound can be used non-invasively to monitor precipitation kinetics ISFIs to better predict vascular embolization.