Synthesis of Biocompatible and X-ray Opaque Iodinated Polymeric Microparticles as an Embolic Material

Abstract

New embolic materials based on 2,3,5-triiodovinyl benzoate (TIVB), vinyl benzoate (VB) and 4-tert-butylbenzoate (VtB) were designed, synthesized and characterized. Polymerization of each monomer was performed in bulk radical polymerization. PVB and PVtB were iodinated via electrophilic aromatic substitution using Selectfluor®. Purity of each product was confirmed by 1H NMR. GPC analysis measured the molecular weight of PTIVB, PVB and PVtB to be 147K, 218K and 262K, respectively with the value of Mw/Mn as 1.18, 1.78 and 3.52, respectively. Formation particle of PTIVB was based on Self-Organized Precipitation (SORP) and microparticles of IPVB as well as IPVtB were prepared using oil in water (O/W) emulsion solvent evaporation method. Microstructure of the particles was observed by an optical microscope after filtered through steel sieves with a pore size of 50, 100 and 200 µm. PTIVB particle size in diameter ranged from 30 to 2000 µm could be prepared by changing the viscosity of PVA solution, concentration of THF and stirring speed in SORP method. On the contrary, microparticles of IPVB and IPVtB prepared by O/W method were irregularly shaped and difficult to control the size, probably due to the low solubility of polymers in organic solvent. Radiopacity of iodinated polymer microparticle was determined under x-ray using C-arm with VisipaqueTM and Lipiodol as controls. Microparticles made of PTIVB showed the highest x-ray opaqueness among the prepared micropaticles, which was strong enough for further application in in vivo study as a contrast agent, while x-ray opaqueness of iodinated PVB was not intense enough to be visualized under x-ray, probably due to a limited number of replaced iodine, and microparticles of IPVtB became highly viscous liquid after iodination.