Gelling process differences in reverse emulsion, in situ gelling polymeric materials for intracranial aneurysm embolization, formulated with injectable contrast agents

Abstract

The use of liquid-to-solid curing materials for brain aneurysm embolization has become increasingly attractive, as liquid embolics can be delivered noninvasively and can potentially achieve a higher degree of aneurysm volume occlusion. This study was aimed at characterizing differences in the gelling process of a reverse emulsion, crosslinking polymer system formulated with different types of injectable contrast agents. The polymeric system consists of poly(propylene glycol) diacrylate (PPODA) and pentaerythritol tetrakis(3-mercaptopropionate) (QT). These monomers undergo Michael-type addition upon initiation by a basic, aqueous solution. Conray™ and Omnipaque™ 300, commercially available contrast agents, were pH-adjusted to basic conditions and used as initiating solutions with the PPODA-QT system. Material characteristics were identified through rheology and scanning electron microscopy (SEM). Results showed that Conray- and Omnipaque-formulated materials progress through the gelling process uniquely, evidenced by distinctly different viscosity profiles and droplet distributions. These results indicate that Conray is more miscible with the PPODA-QT organic phase. Greater solubility in the organic phase allows Conray-formulated gels to have faster and more widespread reaction initiation kinetics when Conray and Omnipaque have the same pH. Omnipaque-formulated gels require a higher pH for the material to solidify in a time frame comparable to Conray-formulated gels. This discrepancy arises because the majority of reaction initiation sites in Omnipaque-formulated gels occur at phase boundaries via hydroxide ion flux from emulsified droplets rather than from hydroxide ions that are solubilized and integrated within the PPODA-QT organic phase.