Polymerization kinetics of n-butyl cyanoacrylate glues used for vascular embolization

Vascular embolization is a minimally invasive treatment used for the management of vascular malformations and tumors. It is carried out under X-ray by navigating a microcatheter into the targeted blood vessel, through which embolic agents are delivered to occlude the vessels. Cyanoacrylate liquid glues have been widely used for vascular embolization owing to their low viscosity, rapid polymerization/solidification rate, good penetration ability and low tissue toxicity. The objective of this study is to quantitatively investigate the physical properties of two n-butyl cyanoacrylate (nBCA) glues (Glubran 2 and Histoacryl) mixed with an iodized oil (Lipiodol) at various concentrations. We show that an homogeneous solution results from the mixing of the glue and Lipiodol, and that the viscosity, density and interfacial tension of the mixture increase with the proportion in Lipiodol. We have designed a new experimental setup to systemically characterize the polymerization kinetics of a glue mixture upon contact with an ionic solution. We observe that the whole polymerization process includes two phases: an interfacial polymerization that takes place at the interface as soon as the two liquids are in contact with a characteristic time scale of the order of the minute; a volumetric polymerization during which a reaction front propagates within the mixture bulk with a characteristic time scale of the order of tens of minutes. The polymerization rate, front propagation speed and volume reduction increase with the glue concentrations. It is the first time that such comprehensive results are obtained on liquid embolic agents.