Developing an in situ forming polyphosphate coacervate as a new liquid embolic agent: From experimental design to pilot animal study

Abstract

A radiopaque temporary liquid embolic agent was synthesized from polyphosphate (PP) coacervates and optimized using a design of experiments approach. Variables studied were: strontium substitution (0-15 mol%), barium substitution (0-15 mol%), PP concentration and degree of polymerization of the polyphosphate (Dp). The viscosity, radiopacity and cell viability of the resulting coacervates were measured for 60 formulations and response surface modeling was used to determine the optimum coacervate that maximized radiopacity and cell viability. The optimum coacervate made from PP with a large Dp (9.5 g NaPP/100mL, 2.2 mol% Sr, 9 mol% Ba and 3.8 mol% Ca) was taken forward to a pilot animal trial. In this rabbit model, PP embolic agent successfully occluded the central auricular artery with promising biocompatibility. Further study is required to optimize the cohesiveness and clinical effectiveness of PP as an in situ setting temporary embolic agent.

Statement of significance: This article describes the development of a new radiopaque temporary liquid embolic agent from the optimization using design of experiments to a pilot animal study. Embolization is a minimally invasive interventional radiology procedure used to block blood flow in a targeted blood vessel. This procedure is used to treat many conditions including: tumors, aneurysms and arteriovenous malformations. Currently, no inherent radiopaque embolic agents are available in the clinic, which would allow for direct imaging of the material during the procedure and follow up treatment.

Keywords: Design of experiments (DOE); Liquid embolic agent; Pilot animal study; Polyphosphate; Radiopaque; Temporary.