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

摘要

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 (D-p). 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 D-p (9.5 g NaPP/100 mL, 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.